Targeting TDP-43 proteinopathy with drugs and drug-like small molecules.
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
31
03
2020
revised:
19
05
2020
accepted:
20
05
2020
pubmed:
30
5
2020
medline:
6
7
2021
entrez:
30
5
2020
Statut:
ppublish
Résumé
Following the discovery of the involvement of the ribonucleoprotein TDP-43 in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), a major research focus has been to develop treatments that can prevent or alleviate these disease conditions. One pharmacological approach has been to use TDP-43-based disease models to test small molecules and drugs already known to have some therapeutic effect in a variety of neurodegenerative conditions. In parallel, various disease models have been used to perform high-throughput screens of drugs and small compound libraries. The aim of this review will be to provide a general overview of the compounds that have been described to alter pathological characteristics of TDP-43. These include expression levels, cytoplasmic mis-localization, post-translational modifications, cleavage, stress granule recruitment and aggregation. In parallel, this review will also address the use of compounds that modify the autophagic/proteasome systems that are known to target TDP-43 misfolding and aggregation. LINKED ARTICLES: This article is part of a themed issue on Neurochemistry in Japan. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.6/issuetoc.
Substances chimiques
DNA-Binding Proteins
0
Pharmaceutical Preparations
0
TARDBP protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1298-1315Subventions
Organisme : Agenzia di Ricerca per la Sclerosi Laterale Amiotrofica
ID : PathensTDP
Informations de copyright
© 2020 The British Pharmacological Society.
Références
Aaron, C., Beaudry, G., Parker, J. A., & Therrien, M. (2016). Maple syrup decreases TDP-43 proteotoxicity in a Caenorhabditis elegans model of amyotrophic lateral sclerosis (ALS). Journal of Agricultural and Food Chemistry, 64, 3338-3344.
Akamatsu, M., Yamashita, T., Hirose, N., Teramoto, S., & Kwak, S. (2016). The AMPA receptor antagonist perampanel robustly rescues amyotrophic lateral sclerosis (ALS) pathology in sporadic ALS model mice. Scientific Reports, 6, 28649. https://doi.org/10.1038/srep28649
Alexander, S. P. H., Cidlowski, J. A., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., … CGTP Collaborators. (2019). THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Nuclear hormone receptors. British Journal of Pharmacology, 176, S229-S246. https://doi.org/10.1111/bph.14750
Alexander, S. P. H., Fabbro, D., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., … CGTP Collaborators. (2019a). THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Catalytic receptors. British Journal of Pharmacology, 176, S247-S296. https://doi.org/10.1111/bph.14751
Alexander, S. P. H., Fabbro, D., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., … CGTP Collaborators. (2019b). THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Enzymes. British Journal of Pharmacology, 176, S297-S396. https://doi.org/10.1111/bph.14752
Alexander, S. P. H., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Faccenda, E., … CGTP Collaborators. (2019). THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Other Protein Targets. British Journal of Pharmacology, 176, S1-S20. https://doi.org/10.1111/bph.14747
Alexander, S. P. H., Mathie, A., Peters, J. A., Veale, E. L., Striessnig, J., Kelly, E., … CGTP Collaborators. (2019). THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology, 176, S142-S228. https://doi.org/10.1111/bph.14749
Alquezar, C., Esteras, N., Encarnacion, A., Moreno, F., de Munain, A. L., & Martin-Requero, A. (2015). Increasing progranulin levels and blockade of the ERK1/2 pathway: Upstream and downstream strategies for the treatment of progranulin deficient frontotemporal dementia. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 25, 386-403. https://doi.org/10.1016/j.euroneuro.2014.12.007
Alquezar, C., Salado, I. G., de la Encarnacion, A., Perez, D. I., Moreno, F., Gil, C., … Martín-Requero, Á. (2016). Targeting TDP-43 phosphorylation by casein kinase-1δ inhibitors: A novel strategy for the treatment of frontotemporal dementia. Molecular Neurodegeneration, 11, 36. https://doi.org/10.1186/s13024-016-0102-7
Archbold, H. C., Jackson, K. L., Arora, A., Weskamp, K., Tank, E. M., Li, X., … Barmada, S. J. (2018). TDP43 nuclear export and neurodegeneration in models of amyotrophic lateral sclerosis and frontotemporal dementia. Scientific Reports, 8, 4606. https://doi.org/10.1038/s41598-018-22858-w
Armstrong, G. A., & Drapeau, P. (2013). Calcium channel agonists protect against neuromuscular dysfunction in a genetic model of TDP-43 mutation in ALS. The Journal of Neuroscience, 33, 1741-1752.
Ash, P. E. A., Dhawan, U., Boudeau, S., Lei, S., Carlomagno, Y., Knobel, M., … Wolozin, B. (2019). Heavy metal neurotoxicants induce ALS-linked TDP-43 pathology. Toxicological Sciences, 167, 105-115. https://doi.org/10.1093/toxsci/kfy267
Ash, P. E. A., Stanford, E. A., Al Abdulatif, A., Ramirez-Cardenas, A., Ballance, H. I., Boudeau, S., … Sherr, D. H. (2017). Dioxins and related environmental contaminants increase TDP-43 levels. Molecular Neurodegeneration, 12, 35. https://doi.org/10.1186/s13024-017-0177-9
Audet, J. N., Soucy, G., & Julien, J. P. (2012). Methylene blue administration fails to confer neuroprotection in two amyotrophic lateral sclerosis mouse models. Neuroscience, 209, 136-143.
Barmada, S. J., Serio, A., Arjun, A., Bilican, B., Daub, A., Ando, D. M., … Finkbeiner, S. (2014). Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models. Nature Chemical Biology, 10, 677-685. https://doi.org/10.1038/nchembio.1563
Bissaro, M., Federico, S., Salmaso, V., Sturlese, M., Spalluto, G., & Moro, S. (2018). Targeting protein kinase CK1δ with riluzole: Could it be one of the possible missing bricks to interpret its effect in the treatment of ALS from a molecular point of view? ChemMedChem, 13, 2601-2605.
Bissaro, M., & Moro, S. (2019). Rethinking to riluzole mechanism of action: The molecular link among protein kinase CK1δ activity, TDP-43 phosphorylation, and amyotrophic lateral sclerosis pharmacological treatment. Neural Regeneration Research, 14, 2083-2085.
Bolognesi, B., Faure, A. J., Seuma, M., Schmiedel, J. M., Tartaglia, G. G., & Lehner, B. (2019). The mutational landscape of a prion-like domain. Nature Communications, 10, 4162.
Borroni, B., Alberici, A., & Buratti, E. (2019). Review: Molecular pathology of frontotemporal lobar degenerations. Neuropathology and Applied Neurobiology, 45, 41-57.
Bose, P., Tremblay, E., Maois, C., Narasimhan, V., Armstrong, G. A. B., Liao, M., … Drapeau, P. (2019). The novel small molecule TRVA242 stabilizes neuromuscular junction defects in multiple animal models of amyotrophic lateral sclerosis. Neurotherapeutics, 16, 1149-1166. https://doi.org/10.1007/s13311-019-00765-w
Boyd, J. D., Lee-Armandt, J. P., Feiler, M. S., Zaarur, N., Liu, M., Kraemer, B., … Glicksman, M. A. (2014). A high-content screen identifies novel compounds that inhibit stress-induced TDP-43 cellular aggregation and associated cytotoxicity. Journal of Biomolecular Screening, 19, 44-56. https://doi.org/10.1177/1087057113501553
Buratti, E. (2015). Functional significance of TDP-43 mutations in disease. Advances in Genetics, 91, 1-53.
Buratti, E. (2018). TDP-43 post-translational modifications in health and disease. Expert Opinion on Therapeutic Targets, 22, 279-293.
Burkhardt, M. F., Martinez, F. J., Wright, S., Ramos, C., Volfson, D., Mason, M., … Martinez, R. (2013). A cellular model for sporadic ALS using patient-derived induced pluripotent stem cells. Molecular and Cellular Neurosciences, 56C, 355-364.
Caccamo, A., Majumder, S., Deng, J. J., Bai, Y., Thornton, F. B., & Oddo, S. (2009). Rapamycin rescues TDP-43 mislocalization and the associated low molecular mass neurofilament instability. The Journal of Biological Chemistry, 284, 27416-27424.
Caccamo, A., Medina, D. X., & Oddo, S. (2013). Glucocorticoids exacerbate cognitive deficits in TDP-25 transgenic mice via a glutathione-mediated mechanism: Implications for aging, stress and TDP-43 proteinopathies. The Journal of Neuroscience, 33, 906-913.
Caragounis, A., Price, K. A., Soon, C. P., Filiz, G., Masters, C. L., Li, Q. X., … White, A. R. (2010). Zinc induces depletion and aggregation of endogenous TDP-43. Free Radical Biology & Medicine, 48, 1152-1161. https://doi.org/10.1016/j.freeradbiomed.2010.01.035
Cassel, J. A., McDonnell, M. E., Velvadapu, V., Andrianov, V., & Reitz, A. B. (2012). Characterization of a series of 4-aminoquinolines that stimulate caspase-7 mediated cleavage of TDP-43 and inhibit its function. Biochimie, 94, 1974-1981.
Cassel, J. A., & Reitz, A. B. (2013). Ubiquilin-2 (UBQLN2) binds with high affinity to the C-terminal region of TDP-43 and modulates TDP-43 levels in H4 cells: Characterization of inhibition by nucleic acids and 4-aminoquinolines. Biochimica et Biophysica Acta, 1834, 964-971.
Cassiano, C., Esposito, R., Tosco, A., Zampella, A., D'Auria, M. V., Riccio, R., … Monti, M. C. (2014). Heteronemin, a marine sponge terpenoid, targets TDP-43, a key factor in several neurodegenerative disorders. Chemical Communications, 50, 406-408. https://doi.org/10.1039/c3cc45454a
Chang, C. F., Lee, Y. C., Lee, K. H., Lin, H. C., Chen, C. L., Shen, C. J., & Huang, C. C. (2016). Therapeutic effect of berberine on TDP-43-related pathogenesis in FTLD and ALS. Journal of Biomedical Science, 23, 72. https://doi.org/10.1186/s12929-016-0290-z
Chang, H. Y., Hou, S. C., Way, T. D., Wong, C. H., & Wang, I. F. (2013). Heat-shock protein dysregulation is associated with functional and pathological TDP-43 aggregation. Nature Communications, 4, 2757. https://doi.org/10.1038/ncomms3757
Chen, S., Liao, Q., Lu, K., Zhou, J., Huang, C., & Bi, F. (2020). Riluzole exhibits no therapeutic efficacy on a transgenic rat model of amyotrophic lateral sclerosis. Current Neurovascular Research. https://doi.org/10.2174/1567202617666200409125227
Chen, T., Turner, B. J., Beart, P. M., Sheehan-Hennessy, L., Elekwachi, C., & Muyderman, H. (2018). Glutathione monoethyl ester prevents TDP-43 pathology in motor neuronal NSC-34 cells. Neurochemistry International, 112, 278-287. https://doi.org/10.1016/j.neuint.2017.08.009
Chen, Y., Wang, H., Ying, Z., & Gao, Q. (2020). Ibudilast enhances the clearance of SOD1 and TDP-43 aggregates through TFEB-mediated autophagy and lysosomal biogenesis: The new molecular mechanism of ibudilast and its implication for neuroprotective therapy. Biochemical and Biophysical Research Communications, 526, 231-238. https://doi.org/10.1016/j.bbrc.2020.03.051
Cheng, C. W., Lin, M. J., & Shen, C. J. (2015). Rapamycin alleviates pathogenesis of a new Drosophila model of ALS-TDP. Journal of Neurogenetics, 1-47.
Choi, K. J., Tsoi, P. S., Moosa, M. M., Paulucci-Holthauzen, A., Liao, S. J., Ferreon, J. C., & Ferreon, A. C. (2018). A chemical chaperone decouples TDP-43 disordered domain phase separation from fibrillation. Biochemistry, 57, 6822-6826. https://doi.org/10.1021/acs.biochem.8b01051
Chung, C. Y., Shin, H. R., Berdan, C. A., Ford, B., Ward, C. C., Olzmann, J. A., … Nomura, D. K. (2019). Covalent targeting of the vacuolar H(+)-ATPase activates autophagy via mTORC1 inhibition. Nature Chemical Biology, 15, 776-785. https://doi.org/10.1038/s41589-019-0308-4
Chung, Y. H., Lin, C. W., Huang, H. Y., Chen, S. L., Huang, H. J., Sun, Y. C., … Hsieh-Li, H. M. (2020). Targeting inflammation, PHA-767491 shows a broad spectrum in protein aggregation diseases. Journal of Molecular Neuroscience. https://doi.org/10.1007/s12031-020-01521-y
Cohen, T. J., Hwang, A. W., Unger, T., Trojanowski, J. Q., & Lee, V. M. (2011). Redox signalling directly regulates TDP-43 via cysteine oxidation and disulphide cross-linking. The EMBO Journal, 31(5), 1241-1252.
Colombrita, C., Zennaro, E., Fallini, C., Weber, M., Sommacal, A., Buratti, E., … Ratti, A. (2009). TDP-43 is recruited to stress granules in conditions of oxidative insult. Journal of Neurochemistry, 111, 1051-1061.
Cox, P. A., & Sacks, O. W. (2002). Cycad neurotoxins, consumption of flying foxes, and ALS-PDC disease in Guam. Neurology, 58, 956-959.
Crippa, V., D'Agostino, V. G., Cristofani, R., Rusmini, P., Cicardi, M. E., Messi, E., … Meroni, M. (2016). Transcriptional induction of the heat shock protein B8 mediates the clearance of misfolded proteins responsible for motor neuron diseases. Scientific Reports, 6, 22827. https://doi.org/10.1038/srep22827
Cristobo, I., Larriba, M. J., Rios, V. D., Garcia, F., Munoz, A., & Casal, J. I. (2011). Proteomic analysis of 1α,25-dihydroxyvitamin D(3) action on human colon cancer cells reveals a link to splicing regulation. Journal of Proteomics, 75, 384-397. https://doi.org/10.1016/j.jprot.2011.08.003
Dang, T. N., Dobson-Stone, C., Glaros, E. N., Kim, W. S., Hallupp, M., Bartley, L., … Schofield, P. R. (2013). Endogenous progesterone levels and frontotemporal dementia: Modulation of TDP-43 and Tau levels in vitro and treatment of the A315T TARDBP mouse model. Disease Models & Mechanisms, 6, 1198-1204. https://doi.org/10.1242/dmm.011460
Dardis, A., Zampieri, S., Canterini, S., Newell, K. L., Stuani, C., Murrell, J. R., … Buratti, E. (2016). Altered localization and functionality of TAR DNA binding protein 43 (TDP-43) in Niemann-Pick disease type C. Acta Neuropathologica Communications, 4, 52. https://doi.org/10.1186/s40478-016-0325-4
Dasuri, K., Ebenezer, P. J., Uranga, R. M., Gavilan, E., Zhang, L., Fernandez-Kim, S. O., … Keller, J. N. (2011). Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulation. Journal of Neuroscience Research, 89, 1471-1477. https://doi.org/10.1002/jnr.22677
Davis, D. A., Cox, P. A., Banack, S. A., Lecusay, P. D., Garamszegi, S. P., Hagan, M. J., … Mash, D. C. (2020). l-Serine reduces spinal cord pathology in a vervet model of preclinical ALS/MND. Journal of Neuropathology and Experimental Neurology, 79, 393-406. https://doi.org/10.1093/jnen/nlaa002
De Marco, G., Lomartire, A., Mandili, G., Lupino, E., Buccinna, B., Ramondetti, C., … Rinaudo, M. T. (2014). Reduced cellular Ca2+ availability enhances TDP-43 cleavage by apoptotic caspases. Biochimica et Biophysica Acta, 1843, 725-734. https://doi.org/10.1016/j.bbamcr.2014.01.010
Dewey, C. M., Cenik, B., Sephton, C. F., Dries, D. R., Mayer, P. 3rd, Good, S. K., … Yu, G. (2011). TDP-43 is directed to stress granules by sorbitol, a novel physiological osmotic and oxidative stressor. Molecular and Cellular Biology, 31, 1098-1108. https://doi.org/10.1128/MCB.01279-10
Dong, H., Xu, L., Wu, L., Wang, X., Duan, W., Li, H., & Li, C. (2014). Curcumin abolishes mutant TDP-43 induced excitability in a motoneuron-like cellular model of ALS. Neuroscience, 272, 141-153. https://doi.org/10.1016/j.neuroscience.2014.04.032
Dormann, D., Capell, A., Carlson, A. M., Shankaran, S. S., Rodde, R., Neumann, M., … Haass, C. (2009). Proteolytic processing of TAR DNA binding protein-43 by caspases produces C-terminal fragments with disease defining properties independent of progranulin. Journal of Neurochemistry, 110, 1082-1094. https://doi.org/10.1111/j.1471-4159.2009.06211.x
Duan, W., Guo, Y., Xiao, J., Chen, X., Li, Z., Han, H., & Li, C. (2013). Neuroprotection by monocarbonyl dimethoxycurcumin C: Ameliorating the toxicity of mutant TDP-43 via HO-1. Molecular Neurobiology, 49(1), 368-379.
Duan, W., Li, X., Shi, J., Guo, Y., Li, Z., & Li, C. (2010). Mutant TAR DNA-binding protein-43 induces oxidative injury in motor neuron-like cell. Neuroscience, 169, 1621-1629.
Dupuis, L., Dengler, R., Heneka, M. T., Meyer, T., Zierz, S., Kassubek, J., … the GERP ALS Study Group. (2012). A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis. PLoS ONE, 7, e37885. https://doi.org/10.1371/journal.pone.0037885
Dutta, K., Patel, P., Rahimian, R., Phaneuf, D., & Julien, J. P. (2017). Withania somnifera reverses transactive response DNA binding protein 43 proteinopathy in a mouse model of amyotrophic lateral sclerosis/frontotemporal lobar degeneration. Neurotherapeutics, 14, 447-462.
Egawa, N., Kitaoka, S., Tsukita, K., Naitoh, M., Takahashi, K., Yamamoto, T., … Aoi, T. (2012). Drug screening for ALS using patient-specific induced pluripotent stem cells. Science Translational Medicine, 4145ra104, 145ra104. https://doi.org/10.1126/scitranslmed.3004052
Espejo-Porras, F., Garcia-Toscano, L., Rodriguez-Cueto, C., Santos-Garcia, I., de Lago, E., & Fernandez-Ruiz, J. (2018). Targeting glial cannabinoid CB2 receptors to delay the progression of the pathological phenotype in TDP-43 (A315T) transgenic mice, a model of amyotrophic lateral sclerosis. British Journal of Pharmacology, 176(10), 1585-1600.
Fang, H. Y., Chen, S. B., Guo, D. J., Pan, S. Y., & Yu, Z. L. (2011). Proteomic identification of differentially expressed proteins in curcumin-treated MCF-7 cells. Phytomedicine, 18, 697-703.
Fang, M. Y., Markmiller, S., Vu, A. Q., Javaherian, A., Dowdle, W. E., Jolivet, P., … Linsley, J. W. (2019). Small-molecule modulation of TDP-43 recruitment to stress granules prevents persistent TDP-43 accumulation in ALS/FTD. Neuron, 103, 802, e811-819.
Festa, C., Cassiano, C., D'Auria, M. V., Debitus, C., Monti, M. C., & De Marino, S. (2014). Scalarane sesterterpenes from Thorectidae sponges as inhibitors of TDP-43 nuclear factor. Organic & Biomolecular Chemistry, 12, 8646-8655. https://doi.org/10.1039/C4OB01510J
Francois-Moutal, L., Felemban, R., Scott, D. D., Sayegh, M. R., Miranda, V. G., Perez-Miller, S., … Khanna, M. (2019). Small molecule targeting TDP-43's RNA recognition motifs reduces locomotor defects in a Drosophila model of amyotrophic lateral sclerosis (ALS). ACS Chemical Biology, 14, 2006-2013. https://doi.org/10.1021/acschembio.9b00481
Fujimori, K., Ishikawa, M., Otomo, A., Atsuta, N., Nakamura, R., Akiyama, T., … Okano, H. (2018). Modeling sporadic ALS in iPSC-derived motor neurons identifies a potential therapeutic agent. Nature Medicine, 24, 1579-1589. https://doi.org/10.1038/s41591-018-0140-5
Gao, J., Wang, L., Gao, C., Arakawa, H., Perry, G., & Wang, X. (2020). TDP-43 inhibitory peptide alleviates neurodegeneration and memory loss in an APP transgenic mouse model for Alzheimer's disease. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1866, 165580.
Girdhar, A., Bharathi, V., Tiwari, V. R., Abhishek, S., Deeksha, W., Mahawar, U. S., … Patel, B. K. (2020). Computational insights into mechanism of AIM4-mediated inhibition of aggregation of TDP-43 protein implicated in ALS and evidence for in vitro inhibition of liquid-liquid phase separation (LLPS) of TDP-43(2C)-A315T by AIM4. International Journal of Biological Macromolecules, 147, 117-130. https://doi.org/10.1016/j.ijbiomac.2020.01.032
Gregory, J. M., Barros, T. P., Meehan, S., Dobson, C. M., & Luheshi, L. M. (2012). The aggregation and neurotoxicity of TDP-43 and its ALS-associated 25 kDa fragment are differentially affected by molecular chaperones in Drosophila. PLoS ONE, 7, e31899. https://doi.org/10.1371/journal.pone.0031899
Hans, F., Glasebach, H., & Kahle, P. J. (2020). Multiple distinct pathways lead to hyperubiquitylated insoluble TDP-43 protein independent of its translocation into stress granules. The Journal of Biological Chemistry, 295, 673-689. https://doi.org/10.1074/jbc.RA119.010617
Harding, S. D., Sharman, J. L., Faccenda, E., Southan, C., Pawson, A. J., Ireland, S., … NC-IUPHAR. (2018). The IUPHAR/BPS guide to pharmacology in 2018: Updates and expansion to encompass the new guide to immunopharmacology. Nucleic Acids Research, 46, D1091-D1106. https://doi.org/10.1093/nar/gkx1121
Heyburn, L., Hebron, M. L., Smith, J., Winston, C., Bechara, J., Li, Z., … Moussa, C. E. H. (2016). Tyrosine kinase inhibition reverses TDP-43 effects on synaptic protein expression, astrocytic function and amino acid dis-homeostasis. Journal of Neurochemistry, 139, 610-623. https://doi.org/10.1111/jnc.13763
Hicks, D. A., Cross, L. L., Williamson, R., & Rattray, M. (2020). Endoplasmic reticulum stress signalling induces casein kinase 1-dependent formation of cytosolic TDP-43 inclusions in motor neuron-like cells. Neurochemical Research, 45, 1354-1364. https://doi.org/10.1007/s11064-019-02832-2
Hogg, M. C., Halang, L., Woods, I., Coughlan, K. S., & Prehn, J. H. M. (2018). Riluzole does not improve lifespan or motor function in three ALS mouse models. Amyotroph Lateral Scler Frontotemporal Degener, 19, 438-445. https://doi.org/10.1080/21678421.2017.1407796
Hu, W., Liu, X., Wang, S., Sun, G., Zhao, R., & Lu, H. (2019). SecinH3 attenuates TDP-43 p.Q331K-induced neuronal toxicity by suppressing endoplasmic reticulum stress and enhancing autophagic flux. IUBMB Life, 71, 192-199.
Huang, H., Zhang, Z. F., Qin, F. W., Tang, W., Liu, D. H., Wu, P. Y., & Jiao, F. (2019). Icariin inhibits chondrocyte apoptosis and angiogenesis by regulating the TDP-43 signaling pathway. Molecular Genetics & Genomic Medicine, 7, e00586. https://doi.org/10.1002/mgg3.586
Huang, S. L., Wu, L. S., Lee, M., Chang, C. W., Cheng, W. C., Fang, Y. S., … Shen, C. K. J. (2020). A robust TDP-43 knock-in mouse model of ALS. Acta Neuropathologica Communications, 8, 3. https://doi.org/10.1186/s40478-020-0881-5
Iguchi, Y., Katsuno, M., Takagi, S., Ishigaki, S., Niwa, J. I., Hasegawa, M., … Sobue, G. (2011). Oxidative stress induced by glutathione depletion reproduces pathological modifications of TDP-43 linked to TDP-43 proteinopathies. Neurobiology of Disease, 45(3), 862-870.
Imamura, K., Izumi, Y., Watanabe, A., Tsukita, K., Woltjen, K., Yamamoto, T., … Inoue, H. (2017). The Src/c-Abl pathway is a potential therapeutic target in amyotrophic lateral sclerosis. Science Translational Medicine, 9, eaaf3962. https://doi.org/10.1126/scitranslmed.aaf3962
Jiang, Y., Choi, W. H., Lee, J. H., Han, D. H., Kim, J. H., Chung, Y. S., … Lee, M. J. (2014). A neurostimulant para-chloroamphetamine inhibits the arginylation branch of the N-end rule pathway. Scientific Reports, 4, 6344.
Jo, M., Lee, S., Kim, K., Lee, S., Kim, S. R., & Kim, H. J. (2019). Inhibition of MEK5 suppresses TDP-43 toxicity via the mTOR-independent activation of the autophagy-lysosome pathway. Biochemical and Biophysical Research Communications, 513, 925-932.
Joardar, A., Menzl, J., Podolsky, T. C., Manzo, E., Estes, P. S., Ashford, S., & Zarnescu, D. C. (2014). PPARγ activation is neuroprotective in a Drosophila model of ALS based on TDP-43. Human Molecular Genetics, 24(6), 1741-1754.
Jung, E. J., Chung, K. H., Bae, D. W., & Kim, C. W. (2016). Proteomic analysis of novel targets associated with the enhancement of TrkA-induced SK-N-MC cancer cell death caused by NGF. Experimental & Molecular Medicine, 48, e235. https://doi.org/10.1038/emm.2016.33
Kabuta, C., Kono, K., Wada, K., & Kabuta, T. (2015). 4-Hydroxynonenal induces persistent insolubilization of TDP-43 and alters its intracellular localization. Biochemical and Biophysical Research Communications, 463, 82-87. https://doi.org/10.1016/j.bbrc.2015.05.027
Karlsson, O., Berg, A. L., Hanrieder, J., Arnerup, G., Lindstrom, A. K., & Brittebo, E. B. (2014). Intracellular fibril formation, calcification, and enrichment of chaperones, cytoskeletal, and intermediate filament proteins in the adult hippocampus CA1 following neonatal exposure to the nonprotein amino acid BMAA. Archives of Toxicology, 89(3), 423-436.
Khosravi, B., LaClair, K. D., Riemenschneider, H., Zhou, Q., Frottin, F., Mareljic, N., … Arzberger, T. (2020). Cell-to-cell transmission of C9orf72 poly-(Gly-Ala) triggers key features of ALS/FTD. The EMBO Journal, 39, e102811.
Kim, H. J., Raphael, A. R., LaDow, E. S., McGurk, L., Weber, R. A., Trojanowski, J. Q., … Bonini, N. M. (2014). Therapeutic modulation of eIF2α phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models. Nature Genetics, 46, 152-160. https://doi.org/10.1038/ng.2853
Kreiter, N., Pal, A., Lojewski, X., Corcia, P., Naujock, M., Reinhardt, P., … Hermann, A. (2018). Age-dependent neurodegeneration and organelle transport deficiencies in mutant TDP43 patient-derived neurons are independent of TDP43 aggregation. Neurobiology of Disease, 115, 167-181. https://doi.org/10.1016/j.nbd.2018.03.010
Lai, C. Y., Liu, Y. J., Lai, H. L., Chen, H. M., Kuo, H. C., Liao, Y. P., & Chern, Y. (2018). The D2 dopamine receptor interferes with the protective effect of the A2A adenosine receptor on TDP-43 mislocalization in experimental models of motor neuron degeneration. Frontiers in Neuroscience, 12, 187. https://doi.org/10.3389/fnins.2018.00187
Laos, V., Bishop, D., Lang, C. A., Marsh, N. M., Cantrell, K. L., Buratto, S. K., … Bowers, M. T. (2020). Modulating ALS-related amyloidogenic TDP-43307-319 oligomeric aggregates with computationally derived therapeutic molecules. Biochemistry, 59, 499-508. https://doi.org/10.1021/acs.biochem.9b00905
Lee, B. H., Lee, M. J., Park, S., Oh, D. C., Elsasser, S., Chen, P. C., … Finley, D. (2010). Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature, 467, 179-184. https://doi.org/10.1038/nature09299
Lee, S., Lee, T. A., Lee, E., Kang, S., Park, A., Kim, S. W., … Park, B. (2015). Identification of a subnuclear body involved in sequence-specific cytokine RNA processing. Nature Communications, 6, 5791. https://doi.org/10.1038/ncomms6791
Leggett, C., McGehee, D. S., Mastrianni, J., Yang, W., Bai, T., & Brorson, J. R. (2012). Tunicamycin produces TDP-43 cytoplasmic inclusions in cultured brain organotypic slices. Journal of the Neurological Sciences, 317, 66-73.
Lei, Y., Zhang, Z. F., Lei, R. X., Wang, S., Zhuang, Y., Liu, A. C., … Zheng, M. (2018). DJ-1 suppresses cytoplasmic TDP-43 aggregation in oxidative stress-induced cell injury. Journal of Alzheimer's Disease: JAD, 66, 1001-1014. https://doi.org/10.3233/JAD-180460
Liachko, N. F., McMillan, P. J., Guthrie, C. R., Bird, T. D., Leverenz, J. B., & Kraemer, B. C. (2013). CDC7 inhibition blocks pathological TDP-43 phosphorylation and neurodegeneration. Annals of Neurology, 74, 39-52.
Libonati, L., Onesti, E., Gori, M. C., Ceccanti, M., Cambieri, C., Fabbri, A., … Inghilleri, M. (2017). Vitamin D in amyotrophic lateral sclerosis. Functional Neurology, 32, 35-40. https://doi.org/10.11138/FNeur/2017.32.1.035
Lin, T. W., Chen, M. T., Lin, L. T., Huang, P. I., Lo, W. L., Yang, Y. P., … Wu, C. W. (2017). TDP-43/HDAC6 axis promoted tumor progression and regulated nutrient deprivation-induced autophagy in glioblastoma. Oncotarget, 8(34), 56612-56625. https://doi.org/10.18632/oncotarget.17979
Liu, C., Leng, B., Li, Y., Jiang, H., Duan, W., Guo, Y., … Hong, K. (2018). Diallyl trisulfide protects motor neurons from the neurotoxic protein TDP-43 via activating lysosomal degradation and the antioxidant response. Neurochemical Research, 43, 2304-2312. https://doi.org/10.1007/s11064-018-2651-3
Liu, Y., Duan, W., Guo, Y., Li, Z., Han, H., Zhang, S., … Li, C. (2014). A new cellular model of pathological TDP-43: The neurotoxicity of stably expressed CTF25 of TDP-43 depends on the proteasome. Neuroscience, 281, 88-98. https://doi.org/10.1016/j.neuroscience.2014.09.043
Llewellyn, K. J., Nalbandian, A., Weiss, L. N., Chang, I., Yu, H., Khatib, B., … Kimonis, V. E. (2017). Myogenic differentiation of VCP disease-induced pluripotent stem cells: A novel platform for drug discovery. PLoS ONE, 12e0176919. https://doi.org/10.1371/journal.pone.0176919
Lokireddy, S., Kukushkin, N. V., & Goldberg, A. L. (2015). cAMP-induced phosphorylation of 26S proteasomes on Rpn6/PSMD11 enhances their activity and the degradation of misfolded proteins. Proceedings of the National Academy of Sciences of the United States of America, 112, E7176-E7185.
Lu, J., Duan, W., Guo, Y., Jiang, H., Li, Z., Huang, J., … Li, C. (2012). Mitochondrial dysfunction in human TDP-43 transfected NSC34 cell lines and the protective effect of dimethoxy curcumin. Brain Research Bulletin, 89, 185-190. https://doi.org/10.1016/j.brainresbull.2012.09.005
Luty, A. A., Kwok, J. B., Dobson-Stone, C., Loy, C. T., Coupland, K. G., Karlstrom, H., … Panegyres, P. K. (2010). Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration-motor neuron disease. Annals of Neurology, 68, 639-649. https://doi.org/10.1002/ana.22274
Maccioni, R., Setzu, M. D., Talani, G., Solari, P., Kasture, A., Sucic, S., … Liscia, A. (2018). Standardized phytotherapic extracts rescue anomalous locomotion and electrophysiological responses of TDP-43 Drosophila melanogaster model of ALS. Scientific Reports, 8, 16002. https://doi.org/10.1038/s41598-018-34452-1
Martinez-Gonzalez, L., Rodriguez-Cueto, C., Cabezudo, D., Bartolome, F., Andres-Benito, P., Ferrer, I., … de Lago, E. (2020). Motor neuron preservation and decrease of in vivo TDP-43 phosphorylation by protein CK-1δ kinase inhibitor treatment. Scientific Reports, 10, 4449.
McDonald, K. K., Aulas, A., Destroismaisons, L., Pickles, S., Beleac, E., Camu, W., … Vande Velde, C. (2011). TAR DNA-binding protein 43 (TDP-43) regulates stress granule dynamics via differential regulation of G3BP and TIA-1. Human Molecular Genetics, 20, 1400-1410.
McGurk, L., Mojsilovic-Petrovic, J., Van Deerlin, V. M., Shorter, J., Kalb, R. G., Lee, V. M., … Bonini, N. M. (2018). Nuclear poly (ADP-ribose) activity is a therapeutic target in amyotrophic lateral sclerosis. Acta Neuropathologica Communications, 6, 84. https://doi.org/10.1186/s40478-018-0586-1
Meyerowitz, J., Parker, S. J., Vella, L. J., Ng, D., Price, K. A., Liddell, J. R., … Hasegawa, M. (2011). C-Jun N-terminal kinase controls TDP-43 accumulation in stress granules induced by oxidative stress. Molecular Neurodegeneration, 6, 57. https://doi.org/10.1186/1750-1326-6-57
Mompean, M., Ramirez de Mingo, D., Hervas, R., Fernandez-Ramirez, M. D. C., Carrion-Vazquez, M., & Laurents, D. V. (2019). Molecular mechanism of the inhibition of TDP-43 amyloidogenesis by QBP1. Archives of Biochemistry and Biophysics, 675, 108113.
Mouhid Al-Achbili, L., Moreno-Ortega, A. J., Matias-Guiu, J., Cano-Abad, M. F., & Ruiz-Nuno, A. (2016). ITH33/IQM9.21 provides neuroprotection in a novel ALS model based on TDP-43 and Na+/Ca2+ overload induced by VTD. Neuroscience Letters, 633, 28-32. https://doi.org/10.1016/j.neulet.2016.09.009
Munoz-Saez, E., de Munck, E., Arahuetes, R. M., Solas, M. T., Martinez, A. M., & Miguel, B. G. (2013). β-N-methylamino-l-alanine induces changes in both GSK3 and TDP-43 in human neuroblastoma. The Journal of Toxicological Sciences, 38, 425-430. https://doi.org/10.2131/jts.38.425
Munoz-Saez, E., de Munck, G. E., Arahuetes Portero, R. M., Martinez, A., Solas Alados, M. T., & Miguel, B. G. (2015). Analysis of β-N-methylamino-l-alanine (l-BMAA) neurotoxicity in rat cerebellum. Neurotoxicology, 48, 192-205. https://doi.org/10.1016/j.neuro.2015.04.001
Murata, H., Hattori, T., Maeda, H., Takashiba, S., Takigawa, M., Kido, J., & Nagata, T. (2015). Identification of transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) as a novel factor for TNF-α expression upon lipopolysaccharide stimulation in human monocytes. Journal of Periodontal Research, 50, 452-460. https://doi.org/10.1111/jre.12227
Nalbandian, A., Llewellyn, K. J., Nguyen, C., Yazdi, P. G., & Kimonis, V. E. (2015). Rapamycin and chloroquine: The in vitro and in vivo effects of autophagy-modifying drugs show promising results in valosin containing protein multisystem proteinopathy. PLoS ONE, 10, e0122888. https://doi.org/10.1371/journal.pone.0122888
Nan, Y. N., Zhu, J. Y., Tan, Y., Zhang, Q., Jia, W., & Hua, Q. (2014). Staurosporine induced apoptosis rapidly downregulates TDP- 43 in glioma cells. Asian Pacific Journal of Cancer Prevention : APJCP, 15, 3575-3579.
Narayan, M., Peralta, D. A., Gibson, C., Zitnyar, A., & Jinwal, U. K. (2015). An optimized InCell Western screening technique identifies hexachlorophene as a novel potent TDP43 targeting drug. Journal of Biotechnology, 207, 34-38. https://doi.org/10.1016/j.jbiotec.2015.04.012
Naviaux, J. C., Wang, L., Li, K., Bright, A. T., Alaynick, W. A., Williams, K. R., … Naviaux, R. K. (2015). Antipurinergic therapy corrects the autism-like features in the fragile X (Fmr1 knockout) mouse model. Mol Autism, 6, 1. https://doi.org/10.1186/2040-2392-6-1
Nshogoza, G., Liu, Y., Gao, J., Liu, M., Moududee, S. A., Ma, R., … Ruan, K. (2019). NMR fragment-based screening against tandem RNA recognition motifs of TDP-43. International Journal of Molecular Sciences, 20, 3230. https://doi.org/10.3390/ijms20133230
Oberstadt, M., Stieler, J., Simpong, D. L., Romuss, U., Urban, N., Schaefer, M., … Holzer, M. (2018). TDP-43 self-interaction is modulated by redox-active compounds auranofin, chelerythrine and riluzole. Scientific Reports, 8, 2248. https://doi.org/10.1038/s41598-018-20565-0
Oh, J., & Lee, N. M. (2017). Schizandrin reduces cytoplasmic TDP-43 accumulation in hippocampal neuronal cells. Biotechnology and Bioprocess Engineering, 22, 9-13. https://doi.org/10.1007/s12257-016-0656-9
Ohuchi, K., Ono, Y., Joho, M., Tsuruma, K., Ogami, S., Yamane, S., … Shimazawa, M. (2018). A docosahexaenoic acid-derived pro-resolving agent, maresin 1, protects motor neuron cells death. Neurochemical Research, 43, 1413-1423. https://doi.org/10.1007/s11064-018-2556-1
Ortuno, D., Carlisle, H. J., & Miller, S. (2016). Does inactivation of USP14 enhance degradation of proteasomal substrates that are associated with neurodegenerative diseases? F1000Res 5. 137.
Pamphlett, R., & Kum Jew, S. (2011). Inorganic mercury within motor neurons does not cause the TDP-43 changes seen in sporadic ALS. Toxicology Letters, 201, 58-61. https://doi.org/10.1016/j.toxlet.2010.12.005
Parker, S. J., Meyerowitz, J., James, J. L., Liddell, J. R., Nonaka, T., Hasegawa, M., … White, A. R. (2012). Inhibition of TDP-43 accumulation by bis(thiosemicarbazonato)-copper complexes. PLoS ONE, 7, e42277. https://doi.org/10.1371/journal.pone.0042277
Posa, D., Martinez-Gonzalez, L., Bartolome, F., Nagaraj, S., Porras, G., Martinez, A., & Martín-Requero, Á. (2019). Recapitulation of pathological TDP-43 features in immortalized lymphocytes from sporadic ALS patients. Molecular Neurobiology, 56, 2424-2432. https://doi.org/10.1007/s12035-018-1249-8
Prasad, A., Raju, G., Sivalingam, V., Girdhar, A., Verma, M., Vats, A., … Patel, B. K. (2016). An acridine derivative, [4,5-bis{(N-carboxy methyl imidazolium)methyl}acridine] dibromide, shows anti-TDP-43 aggregation effect in ALS disease models. Scientific Reports, 6, 39490. https://doi.org/10.1038/srep39490
Rojas, F., Gonzalez, D., Cortes, N., Ampuero, E., Hernandez, D. E., Fritz, E., … Van Zundert, B. (2015). Reactive oxygen species trigger motoneuron death in non-cell-autonomous models of ALS through activation of c-Abl signaling. Frontiers in Cellular Neuroscience, 9, 203. https://doi.org/10.3389/fncel.2015.00203
Rusmini, P., Simonini, F., Crippa, V., Bolzoni, E., Onesto, E., Cagnin, M., … Poletti, A. (2011). 17-AAG increases autophagic removal of mutant androgen receptor in spinal and bulbar muscular atrophy. Neurobiology of Disease, 41, 83-95. https://doi.org/10.1016/j.nbd.2010.08.023
Salado, I. G., Redondo, M., Bello, M. L., Perez, C., Liachko, N. F., Kraemer, B. C., … Perez, D. I. (2014). Protein kinase CK-1 inhibitors as new potential drugs for amyotrophic lateral sclerosis. Journal of Medicinal Chemistry, 57, 2755-2772. https://doi.org/10.1021/jm500065f
Schutz, B., Reimann, J., Dumitrescu-Ozimek, L., Kappes-Horn, K., Landreth, G. E., Schurmann, B., … Heneka, M. T. (2005). The oral antidiabetic pioglitazone protects from neurodegeneration and amyotrophic lateral sclerosis-like symptoms in superoxide dismutase-G93A transgenic mice. The Journal of Neuroscience, 25, 7805-7812. https://doi.org/10.1523/JNEUROSCI.2038-05.2005
Scott, L. L., & Downing, T. G. (2017). A single neonatal exposure to BMAA in a rat model produces neuropathology consistent with neurodegenerative diseases. Toxins (Basel), 10, 22. https://doi.org/10.3390/toxins10010022
Scotter, E. L., Vance, C., Nishimura, A. L., Lee, Y. B., Chen, H. J., Urwin, H., … Shaw, C. E. (2014). Differential roles of the ubiquitin proteasome system and autophagy in the clearance of soluble and aggregated TDP-43 species. Journal of Cell Science, 127, 1263-1278. https://doi.org/10.1242/jcs.140087
Tardiff, D. F., Tucci, M. L., Caldwell, K. A., Caldwell, G. A., & Lindquist, S. (2011). Different 8-hydroxyquinolines protect models of TDP-43, α-synuclein, and polyglutamine proteotoxicity through distinct mechanisms. The Journal of Biological Chemistry, 287, 4107-4120. https://doi.org/10.1074/jbc.M111.308668
Tian, K. W., Jiang, H., Wang, B. B., Zhang, F., & Han, S. (2016). Intravenous injection of l-BMAA induces a rat model with comprehensive characteristics of amyotrophic lateral sclerosis/Parkinson-dementia complex. Toxicol Res (Camb), 5, 79-96.
Tran, L. T., Gentil, B. J., Sullivan, K. E., & Durham, H. D. (2014). The voltage-gated calcium channel blocker lomerizine is neuroprotective in motor neurons expressing mutant SOD1, but not TDP-43. Journal of Neurochemistry, 130, 455-466. https://doi.org/10.1111/jnc.12738
Urushitani, M., Sato, T., Bamba, H., Hisa, Y., & Tooyama, I. (2010). Synergistic effect between proteasome and autophagosome in the clearance of polyubiquitinated TDP-43. Journal of Neuroscience Research, 88, 784-797. https://doi.org/10.1002/jnr.22243
Ustyugov, A., Shevtsova, E., & Bachurin, S. (2015). Novel sites of neuroprotective action of dimebon (Latrepirdine). Molecular Neurobiology, 52, 970-978. https://doi.org/10.1007/s12035-015-9249-4
Vaccaro, A., Patten, S. A., Aggad, D., Julien, C., Maios, C., Kabashi, E., … Parker, J. A. (2013). Pharmacological reduction of ER stress protects against TDP-43 neuronal toxicity in vivo. Neurobiology of Disease, 55, 64-75. https://doi.org/10.1016/j.nbd.2013.03.015
Vaccaro, A., Patten, S. A., Ciura, S., Maios, C., Therrien, M., Drapeau, P., … Parker, J. A. (2012). Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio. PLoS ONE, 7, e42117. https://doi.org/10.1371/journal.pone.0042117
van Eersel, J., Ke, Y. D., Gladbach, A., Bi, M., Gotz, J., Kril, J. J., & Van Eersel, J. (2011). Cytoplasmic accumulation and aggregation of TDP-43 upon proteasome inhibition in cultured neurons. PLoS ONE, 6, e22850. https://doi.org/10.1371/journal.pone.0022850
Vieira, F. G., LaDow, E., Moreno, A., Kidd, J. D., Levine, B., Thompson, K., … Perrin, S. (2014). Dexpramipexole is ineffective in two models of ALS related neurodegeneration. PLoS ONE, 9, e91608. https://doi.org/10.1371/journal.pone.0091608
Walker, A. K., Soo, K. Y., Sundaramoorthy, V., Parakh, S., Ma, Y., Farg, M. A., … Atkin, J. D. (2013). ALS-associated TDP-43 induces endoplasmic reticulum stress, which drives cytoplasmic TDP-43 accumulation and stress granule formation. PLoS ONE, 8, e81170. https://doi.org/10.1371/journal.pone.0081170
Wang, I. F., Chang, H. Y., Hou, S. C., Liou, G. G., Way, T. D., & James Shen, C. K. (2012). The self-interaction of native TDP-43 C terminus inhibits its degradation and contributes to early proteinopathies. Nature Communications, 3, 766. https://doi.org/10.1038/ncomms1766
Wang, I. F., Guo, B. S., Liu, Y. C., Wu, C. C., Yang, C. H., Tsai, K. J., & Shen, C. K. J. (2012). Autophagy activators rescue and alleviate pathogenesis of a mouse model with proteinopathies of the TAR DNA-binding protein 43. Proceedings of the National Academy of Sciences of the United States of America, 109, 15024-15029. https://doi.org/10.1073/pnas.1206362109
Wang, X., Fan, H., Ying, Z., Li, B., Wang, H., & Wang, G. (2010). Degradation of TDP-43 and its pathogenic form by autophagy and the ubiquitin-proteasome system. Neuroscience Letters, 469, 112-116.
Wang, X., Ma, M., Teng, J., Che, X., Zhang, W., Feng, S., … Ding, X. (2015). Valproate attenuates 25-kDa C-terminal fragment of TDP-43-induced neuronal toxicity via suppressing endoplasmic reticulum stress and activating autophagy. International Journal of Biological Sciences, 11, 752-761. https://doi.org/10.7150/ijbs.11880
Wang, Y., Liu, F. T., Wang, Y. X., Guan, R. Y., Chen, C., Li, D. K., … Wang, J. (2018). Autophagic modulation by trehalose reduces accumulation of TDP-43 in a cell model of amyotrophic lateral sclerosis via TFEB activation. Neurotoxicity Research, 34, 109-120. https://doi.org/10.1007/s12640-018-9865-7
Wenqiang, C., Lonskaya, I., Hebron, M. L., Ibrahim, Z., Olszewski, R. T., Neale, J. H., & Moussa, C. E. H. (2014). Parkin-mediated reduction of nuclear and soluble TDP-43 reverses behavioral decline in symptomatic mice. Human Molecular Genetics, 23, 4960-4969. https://doi.org/10.1093/hmg/ddu211
Wobst, H. J., Delsing, L., Brandon, N. J., & Moss, S. J. (2017). Truncation of the TAR DNA-binding protein 43 is not a prerequisite for cytoplasmic relocalization, and is suppressed by caspase inhibition and by introduction of the A90V sequence variant. PLoS ONE, 12, e0177181. https://doi.org/10.1371/journal.pone.0177181
Wong, S. Q., Pontifex, M. G., Phelan, M. M., Pidathala, C., Kraemer, B. C., Barclay, J. W., … Morgan, A. (2018). α-Methyl-α-phenylsuccinimide ameliorates neurodegeneration in a C. elegans model of TDP-43 proteinopathy. Neurobiology of Disease, 118, 40-54. https://doi.org/10.1016/j.nbd.2018.06.013
Xia, Q., Hu, Q., Wang, H., Yang, H., Gao, F., Ren, H., … Wang, G. (2015). Induction of COX-2-PGE2 synthesis by activation of the MAPK/ERK pathway contributes to neuronal death triggered by TDP-43-depleted microglia. Cell Death & Disease, 6, e1702. https://doi.org/10.1038/cddis.2015.69
Yamashita, M., Nonaka, T., Arai, T., Kametani, F., Buchman, V. L., Ninkina, N., … Hasegawa, M. (2009). Methylene blue and dimebon inhibit aggregation of TDP-43 in cellular models. FEBS Letters, 583, 2419-2424. https://doi.org/10.1016/j.febslet.2009.06.042
Yang, Y. M., Gupta, S. K., Kim, K. J., Powers, B. E., Cerqueira, A., Wainger, B. J., … Rubin, L. L. (2013). A small molecule screen in stem-cell-derived motor neurons identifies a kinase inhibitor as a candidate therapeutic for ALS. Cell Stem Cell, 12, 713-726. https://doi.org/10.1016/j.stem.2013.04.003
Yin, H. Z., Yu, S., Hsu, C. I., Liu, J., Acab, A., Wu, R., … Weiss, J. H. (2014). Intrathecal infusion of BMAA induces selective motor neuron damage and astrogliosis in the ventral horn of the spinal cord. Experimental Neurology, 261, 1-9. https://doi.org/10.1016/j.expneurol.2014.06.003
Zhang, H. X., Tanji, K., Yoshida, H., Hayakari, M., Shibata, T., Mori, F., … Wakabayashi, K. (2010). Alteration of biochemical and pathological properties of TDP-43 protein by a lipid mediator, 15-deoxy-Δ(12,14)-prostaglandin J(2). Experimental Neurology, 222, 296-303. https://doi.org/10.1016/j.expneurol.2010.01.007
Zheng, M., Shi, Y., & Fan, D. (2013). Nuclear TAR DNA-binding protein 43: A new target for amyotrophic lateral sclerosis treatment. Neural Regeneration Research, 8, 3284-3295.
Zhou, F., Dong, H., Liu, Y., Yan, L., Sun, C., Hao, P., … Liu, Y. (2018). Raloxifene, a promising estrogen replacement, limits TDP-25 cell death by enhancing autophagy and suppressing apoptosis. Brain Research Bulletin, 140, 281-290. https://doi.org/10.1016/j.brainresbull.2018.05.017
Zhuang, J., Wen, X., Zhang, Y. Q., Shan, Q., Zhang, Z. F., Zheng, G. H., … Zheng, Y. L. (2017). TDP-43 upregulation mediated by the NLRP3 inflammasome induces cognitive impairment in 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47)-treated mice. Brain, Behavior, and Immunity, 65, 99-110. https://doi.org/10.1016/j.bbi.2017.05.014