PolyGA targets the ER stress-adaptive response by impairing GRP75 function at the MAM in C9ORF72-ALS/FTD.
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
08
05
2022
accepted:
06
09
2022
revised:
18
08
2022
pubmed:
20
9
2022
medline:
12
10
2022
entrez:
19
9
2022
Statut:
ppublish
Résumé
ER stress signaling is linked to the pathophysiological and clinical disease manifestations in amyotrophic lateral sclerosis (ALS). Here, we have investigated ER stress-induced adaptive mechanisms in C9ORF72-ALS/FTD, focusing on uncovering early endogenous neuroprotective mechanisms and the crosstalk between pathological and adaptive responses in disease onset and progression. We provide evidence for the early onset of ER stress-mediated adaptive response in C9ORF72 patient-derived motoneurons (MNs), reflected by the elevated increase in GRP75 expression. These transiently increased GRP75 levels enhance ER-mitochondrial association, boosting mitochondrial function and sustaining cellular bioenergetics during the initial stage of disease, thereby counteracting early mitochondrial deficits. In C9orf72 rodent neurons, an abrupt reduction in GRP75 expression coincided with the onset of UPR, mitochondrial dysfunction and the emergence of PolyGA aggregates, which co-localize with GRP75. Similarly, the overexpression of PolyGA in WT cortical neurons or C9ORF72 patient-derived MNs led to the sequestration of GRP75 within PolyGA inclusions, resulting in mitochondrial calcium (Ca
Identifiants
pubmed: 36121477
doi: 10.1007/s00401-022-02494-5
pii: 10.1007/s00401-022-02494-5
pmc: PMC9547809
doi:
Substances chimiques
C9orf72 Protein
0
C9orf72 protein, human
0
HSP70 Heat-Shock Proteins
0
Membrane Proteins
0
Polyribonucleotides
0
glucose-regulated proteins
0
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
939-966Subventions
Organisme : Medical Research Council
ID : MC_EX_MR/N50192X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N013255/1
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
Références
Božič J, Motaln H, Janež AP, Markič L, Tripathi P, Yamoah A et al (2022) Interactome screening of C9orf72 dipeptide repeats reveals VCP sequestration and functional impairment by polyGA. Brain 145:684–699. https://doi.org/10.1093/brain/awab300
doi: 10.1093/brain/awab300
pubmed: 34534264
Braems E, Swinnen B, van den Bosch L (2020) C9orf72 loss-of-function: a trivial, stand-alone or additive mechanism in C9 ALS/FTD? Acta Neuropathol 140:625–643. https://doi.org/10.1007/s00401-020-02214-x
doi: 10.1007/s00401-020-02214-x
pubmed: 32876811
pmcid: 7547039
Bravo R, Vicencio JM, Parra V, Troncoso R, Munoz JP, Bui M et al (2011) Increased ER-mitochondrial coupling promotes mitochondrial respiration and bioenergetics during early phases of ER stress. J Cell Sci 124:2143–2152. https://doi.org/10.1242/jcs.080762
doi: 10.1242/jcs.080762
pubmed: 21628424
pmcid: 3113668
Brettschneider J, Arai K, del Tredici K, Toledo JB, Robinson JL, Lee EB et al (2014) TDP-43 pathology and neuronal loss in amyotrophic lateral sclerosis spinal cord. Acta Neuropathol 128:423–437. https://doi.org/10.1007/s00401-014-1299-6
doi: 10.1007/s00401-014-1299-6
pubmed: 24916269
pmcid: 4384652
Brettschneider J, del Tredici K, Irwin DJ, Grossman M, Robinson JL, Toledo JB et al (2014) Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD). Acta Neuropathol 127:423–439. https://doi.org/10.1007/s00401-013-1238-y
doi: 10.1007/s00401-013-1238-y
pubmed: 24407427
pmcid: 3971993
Brettschneider J, del Tredici K, Toledo JB, Robinson JL, Irwin DJ, Grossman M et al (2013) Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol 74:20–38. https://doi.org/10.1002/ana.23937
doi: 10.1002/ana.23937
pubmed: 23686809
pmcid: 3785076
Burbulla LF, Fitzgerald JC, Stegen K, Westermeier J, Thost A-K, Kato H et al (2014) Mitochondrial proteolytic stress induced by loss of mortalin function is rescued by Parkin and PINK1. Cell Death Dis 5:e1180–e1180. https://doi.org/10.1038/cddis.2014.103
doi: 10.1038/cddis.2014.103
pubmed: 24743735
pmcid: 4001296
Burbulla LF, Schelling C, Kato H, Rapaport D, Woitalla D, Schiesling C et al (2010) Dissecting the role of the mitochondrial chaperone mortalin in Parkinson’s disease: functional impact of disease-related variants on mitochondrial homeostasis. Hum Mol Genet 19:4437–4452. https://doi.org/10.1093/hmg/ddq370
doi: 10.1093/hmg/ddq370
pubmed: 20817635
pmcid: 3298849
Bush JA, Aikawa H, Fuerst R, Li Y, Ursu A, Meyer SM et al (2021) Ribonuclease recruitment using a small molecule reduced c9ALS/FTD r(G 4 C 2) repeat expansion in vitro and in vivo ALS models. Sci Transl Med. https://doi.org/10.1126/scitranslmed.abd5991
doi: 10.1126/scitranslmed.abd5991
pubmed: 34705518
Calvo-Rodriguez M, Hou SS, Snyder AC, Kharitonova EK, Russ AN, Das S et al (2020) Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer’s disease. Nat Commun 11:2146. https://doi.org/10.1038/s41467-020-16074-2
doi: 10.1038/s41467-020-16074-2
pubmed: 32358564
pmcid: 7195480
Cheng W, Wang S, Mestre AA, Fu C, Makarem A, Xian F et al (2018) C9ORF72 GGGGCC repeat-associated non-AUG translation is upregulated by stress through eIF2α phosphorylation. Nat Commun 9:51. https://doi.org/10.1038/s41467-017-02495-z
doi: 10.1038/s41467-017-02495-z
pubmed: 29302060
pmcid: 5754368
Choi SY, Lopez-Gonzalez R, Krishnan G, Phillips HL, Li AN, Seeley WW et al (2019) C9ORF72-ALS/FTD-associated poly(GR) binds Atp5a1 and compromises mitochondrial function in vivo. Nat Neurosci 22:851–862. https://doi.org/10.1038/s41593-019-0397-0
doi: 10.1038/s41593-019-0397-0
pubmed: 31086314
pmcid: 6800116
Dafinca R, Barbagallo P, Farrimond L, Candalija A, Scaber J, Ababneh NA et al (2020) Impairment of mitochondrial calcium buffering links mutations in C9ORF72 and TARDBP in iPS-derived motor neurons from patients with ALS/FTD. Stem Cell Rep 14:892–908. https://doi.org/10.1016/j.stemcr.2020.03.023
doi: 10.1016/j.stemcr.2020.03.023
Dafinca R, Scaber J, Ababneh N, Lalic T, Weir G, Christian H et al (2016) C9orf72 hexanucleotide expansions are associated with altered endoplasmic reticulum calcium homeostasis and stress granule formation in induced pluripotent stem cell-derived neurons from patients with amyotrophic lateral sclerosis and frontotemporal deme. Stem Cells 34:2063–2078. https://doi.org/10.1002/stem.2388
doi: 10.1002/stem.2388
pubmed: 27097283
DeJesus-Hernandez M, Mackenzie IRR, Boeve BFF, Boxer ALL, Baker M, Rutherford NJJ et al (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72:245–256. https://doi.org/10.1016/j.neuron.2011.09.011
doi: 10.1016/j.neuron.2011.09.011
pubmed: 21944778
pmcid: 3202986
Dirren E, Towne CL, Setola V, Redmond DE, Schneider BL, Aebischer P (2014) Intracerebroventricular injection of adeno-associated virus 6 and 9 vectors for cell type-specific transgene expression in the spinal cord. Hum Gene Ther 25:109–120. https://doi.org/10.1089/hum.2013.021
doi: 10.1089/hum.2013.021
pubmed: 24191919
Dreser A, Vollrath JT, Sechi A, Johann S, Roos A, Yamoah A et al (2017) The ALS-linked E102Q mutation in Sigma receptor-1 leads to ER stress-mediated defects in protein homeostasis and dysregulation of RNA-binding proteins. Cell Death Differ 24:1655–1671. https://doi.org/10.1038/cdd.2017.88
doi: 10.1038/cdd.2017.88
pubmed: 28622300
pmcid: 5596426
Fernández-Fernández MR, Gragera M, Ochoa-Ibarrola L, Quintana-Gallardo L, Valpuesta JM (2017) Hsp70 - a master regulator in protein degradation. FEBS Lett 591:2648–2660. https://doi.org/10.1002/1873-3468.12751
doi: 10.1002/1873-3468.12751
pubmed: 28696498
Filézac de L’Etang A, Maharjan N, Cordeiro Braña M, Ruegsegger C, Rehmann R, Goswami A et al (2015) Marinesco-Sjögren syndrome protein SIL1 regulates motor neuron subtype-selective ER stress in ALS. Nat Neurosci 18:227–238. https://doi.org/10.1038/nn.3903
doi: 10.1038/nn.3903
pubmed: 25559081
Freibaum BD, Taylor JP (2017) The role of dipeptide repeats in C9ORF72-related ALS-FTD. Front Mol Neurosci 10:35. https://doi.org/10.3389/fnmol.2017.00035
doi: 10.3389/fnmol.2017.00035
pubmed: 28243191
pmcid: 5303742
Friedman JR, Nunnari J (2014) Mitochondrial form and function. Nature 505:335–343. https://doi.org/10.1038/nature12985
doi: 10.1038/nature12985
pubmed: 24429632
pmcid: 4075653
Gami-Patel P, Dijken I, Meeter LH, Melhem S, Morrema THJ, Scheper W et al (2021) Unfolded protein response activation in C9orf72 frontotemporal dementia is associated with dipeptide pathology and granulovacuolar degeneration in granule cells. Brain Pathol 31:163–173. https://doi.org/10.1111/bpa.12894
doi: 10.1111/bpa.12894
pubmed: 32865835
Gomez-Suaga P, Mórotz GM, Markovinovic A, Martín-Guerrero SM, Preza E, Arias N et al (2022) Disruption of ER-mitochondria tethering and signalling in C9orf72 -associated amyotrophic lateral sclerosis and frontotemporal dementia. Aging Cell. https://doi.org/10.1111/acel.13549
doi: 10.1111/acel.13549
pubmed: 35026048
pmcid: 8844122
Görlach A, Klappa P, DrT K (2006) The endoplasmic reticulum: folding, calcium homeostasis, signaling, and redox control. Antioxid Redox Signal 8:1391–1418. https://doi.org/10.1089/ars.2006.8.1391
doi: 10.1089/ars.2006.8.1391
pubmed: 16986999
Hetz C, Saxena S (2017) ER stress and the unfolded protein response in neurodegeneration. Nat Rev Neurol 13:477–491. https://doi.org/10.1038/nrneurol.2017.99
doi: 10.1038/nrneurol.2017.99
pubmed: 28731040
Honrath B, Metz I, Bendridi N, Rieusset J, Culmsee C, Dolga AM (2017) Glucose-regulated protein 75 determines ER-mitochondrial coupling and sensitivity to oxidative stress in neuronal cells. Cell Death Discov 3:17076. https://doi.org/10.1038/cddiscovery.2017.76
doi: 10.1038/cddiscovery.2017.76
pubmed: 29367884
pmcid: 5672593
Hoseki J, Ushioda R, Nagata K (2010) Mechanism and components of endoplasmic reticulum-associated degradation. J Biochem 147:19–25. https://doi.org/10.1093/jb/mvp194
doi: 10.1093/jb/mvp194
pubmed: 19923195
Hu W, Qiu B, Guan W, Wang Q, Wang M, Li W et al (2015) Direct conversion of normal and Alzheimer’s disease human fibroblasts into neuronal cells by small molecules. Cell Stem Cell 17:204–212. https://doi.org/10.1016/j.stem.2015.07.006
doi: 10.1016/j.stem.2015.07.006
pubmed: 26253202
Imhof A, Kövari E, von Gunten A, Gold G, Rivara C-B, Herrmann FR et al (2007) Morphological substrates of cognitive decline in nonagenarians and centenarians: a new paradigm? J Neurol Sci 257:72–79. https://doi.org/10.1016/j.jns.2007.01.025
doi: 10.1016/j.jns.2007.01.025
pubmed: 17303173
Jafarinia H, van der Giessen E, Onck PR (2020) Phase separation of toxic dipeptide repeat proteins related to C9orf72 ALS/FTD. Biophys J 119:843–851. https://doi.org/10.1016/j.bpj.2020.07.005
doi: 10.1016/j.bpj.2020.07.005
pubmed: 32730793
pmcid: 7451925
Jin J, Hulette C, Wang Y, Zhang T, Pan C, Wadhwa R et al (2006) Proteomic identification of a stress protein, mortalin/mthsp70/GRP75: relevance to Parkinson disease. Mol Cell Proteomics 5:1193–1204. https://doi.org/10.1074/mcp.M500382-MCP200
doi: 10.1074/mcp.M500382-MCP200
pubmed: 16565515
Kaus A, Sareen D (2015) ALS patient stem cells for unveiling disease signatures of motoneuron susceptibility: perspectives on the deadly mitochondria, ER stress and calcium triad. Front Cell Neurosci 9:448. https://doi.org/10.3389/fncel.2015.00448
doi: 10.3389/fncel.2015.00448
pubmed: 26635528
pmcid: 4652136
Khosravi B, LaClair KD, Riemenschneider H, Zhou Q, Frottin F, Mareljic N et al (2020) Cell-to-cell transmission of C9orf72 poly-(Gly-Ala) triggers key features of ALS/FTD. EMBO J. https://doi.org/10.15252/embj.2019102811
doi: 10.15252/embj.2019102811
pubmed: 32175624
pmcid: 7156967
Kiskinis E, Sandoe J, Williams LAA, Boulting GLL, Moccia R, Wainger BJJ et al (2014) Pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1. Cell Stem Cell 14:781–795. https://doi.org/10.1016/j.stem.2014.03.004
doi: 10.1016/j.stem.2014.03.004
pubmed: 24704492
pmcid: 4653065
Kok E, Haikonen S, Luoto T, Huhtala H, Goebeler S, Haapasalo H et al (2009) Apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begins in middle age. Ann Neurol 65:650–657. https://doi.org/10.1002/ana.21696
doi: 10.1002/ana.21696
pubmed: 19557866
LaClair KD, Zhou Q, Michaelsen M, Wefers B, Brill MS, Janjic A et al (2020) Congenic expression of poly-GA but not poly-PR in mice triggers selective neuron loss and interferon responses found in C9orf72 ALS. Acta Neuropathol 140:121–142. https://doi.org/10.1007/s00401-020-02176-0
doi: 10.1007/s00401-020-02176-0
pubmed: 32562018
pmcid: 7360660
Lau DHW, Hartopp N, Welsh NJ, Mueller S, Glennon EB, Mórotz GM et al (2018) Disruption of ER−mitochondria signalling in fronto-temporal dementia and related amyotrophic lateral sclerosis. Cell Death Dis 9:327. https://doi.org/10.1038/s41419-017-0022-7
doi: 10.1038/s41419-017-0022-7
pubmed: 29491392
pmcid: 5832427
Lee AS (2014) Glucose-regulated proteins in cancer: molecular mechanisms and therapeutic potential. Nat Rev Cancer 14:263–276. https://doi.org/10.1038/nrc3701
doi: 10.1038/nrc3701
pubmed: 24658275
pmcid: 4158750
Lee S, Shang Y, Redmond SAA, Urisman A, Tang AAA, Li KHH et al (2016) Activation of HIPK2 promotes ER stress-mediated neurodegeneration in amyotrophic lateral sclerosis. Neuron 91:41–55. https://doi.org/10.1016/j.neuron.2016.05.021
doi: 10.1016/j.neuron.2016.05.021
pubmed: 27321923
pmcid: 4938715
Liu F, Morderer D, Wren MC, Vettleson-Trutza SA, Wang Y, Rabichow BE et al (2022) Proximity proteomics of C9orf72 dipeptide repeat proteins identifies molecular chaperones as modifiers of poly-GA aggregation. Acta Neuropathol Commun 10:22. https://doi.org/10.1186/s40478-022-01322-x
doi: 10.1186/s40478-022-01322-x
pubmed: 35164882
pmcid: 8842533
Liu Y, Pattamatta A, Zu T, Reid T, Bardhi O, Borchelt DR et al (2016) C9orf72 BAC mouse model with motor deficits and neurodegenerative features of ALS/FTD. Neuron 90:521–534. https://doi.org/10.1016/j.neuron.2016.04.005
doi: 10.1016/j.neuron.2016.04.005
pubmed: 27112499
Lopez-Gonzalez R, Lu Y, Gendron TFF, Karydas A, Tran H, Yang D et al (2016) Poly(GR) in C9ORF72-related ALS/FTD compromises mitochondrial function and increases oxidative stress and DNA damage in iPSC-derived motor neurons. Neuron 92:383–391. https://doi.org/10.1016/j.neuron.2016.09.015
doi: 10.1016/j.neuron.2016.09.015
pubmed: 27720481
pmcid: 5111366
Majounie E, Renton AE, Mok K, Dopper EGP, Waite A, Rollinson S et al (2012) Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol 11:323–330. https://doi.org/10.1016/S1474-4422(12)70043-1
doi: 10.1016/S1474-4422(12)70043-1
pubmed: 22406228
pmcid: 3322422
May S, Hornburg D, Schludi MH, Arzberger T, Rentzsch K, Schwenk BM et al (2014) C9orf72 FTLD/ALS-associated Gly-Ala dipeptide repeat proteins cause neuronal toxicity and Unc119 sequestration. Acta Neuropathol 128:485–503. https://doi.org/10.1007/s00401-014-1329-4
doi: 10.1007/s00401-014-1329-4
pubmed: 25120191
pmcid: 4159571
Mazzoni EO, Mahony S, Closser M, Morrison CA, Nedelec S, Williams DJ et al (2013) Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity. Nat Neurosci 16:1219–1227. https://doi.org/10.1038/nn.3467
doi: 10.1038/nn.3467
pubmed: 23872598
McEachin ZT, Parameswaran J, Raj N, Bassell GJ, Jiang J (2020) RNA-mediated toxicity in C9orf72 ALS and FTD. Neurobiol Dis 145:105055. https://doi.org/10.1016/j.nbd.2020.105055
doi: 10.1016/j.nbd.2020.105055
pubmed: 32829028
pmcid: 7572710
McKenzie M, Lim SC, Duchen MR (2017) Simultaneous measurement of mitochondrial calcium and mitochondrial membrane potential in live cells by fluorescent microscopy. JoVE. https://doi.org/10.3791/55166
doi: 10.3791/55166
pubmed: 28190045
pmcid: 5352290
Mehta AR, Gregory JM, Dando O, Carter RN, Burr K, Nanda J et al (2021) Mitochondrial bioenergetic deficits in C9orf72 amyotrophic lateral sclerosis motor neurons cause dysfunctional axonal homeostasis. Acta Neuropathol 141:257–279. https://doi.org/10.1007/s00401-020-02252-5
doi: 10.1007/s00401-020-02252-5
pubmed: 33398403
pmcid: 7847443
Mertens J, Paquola ACM, Ku M, Hatch E, Böhnke L, Ladjevardi S et al (2015) Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell Stem Cell 17:705–718. https://doi.org/10.1016/j.stem.2015.09.001
doi: 10.1016/j.stem.2015.09.001
pubmed: 26456686
pmcid: 5929130
Meyer K, Ferraiuolo L, Miranda CJ, Likhite S, McElroy S, Renusch S et al (2014) Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS. PNAS 111:829–832. https://doi.org/10.1073/pnas.1314085111
doi: 10.1073/pnas.1314085111
pubmed: 24379375
Mordes DA, Morrison BM, Ament XH, Cantrell C, Mok J, Eggan P et al (2020) Absence of survival and motor deficits in 500 repeat C9ORF72 BAC mice. Neuron 108:775-783.e4. https://doi.org/10.1016/j.neuron.2020.08.009
doi: 10.1016/j.neuron.2020.08.009
pubmed: 33022228
Mori F, Tanji K, Zhang H-X, Nishihira Y, Tan C-F, Takahashi H et al (2008) Maturation process of TDP-43-positive neuronal cytoplasmic inclusions in amyotrophic lateral sclerosis with and without dementia. Acta Neuropathol 116:193–203. https://doi.org/10.1007/s00401-008-0396-9
doi: 10.1007/s00401-008-0396-9
pubmed: 18560845
Nguyen L, Laboissonniere LA, Guo S, Pilotto F, Scheidegger O, Oestmann A et al (2020) Survival and motor phenotypes in FVB C9–500 ALS/FTD BAC transgenic mice reproduced by multiple labs. Neuron 108:784-796.e3. https://doi.org/10.1016/j.neuron.2020.09.009
doi: 10.1016/j.neuron.2020.09.009
pubmed: 33022226
pmcid: 8281452
Oda T, Kosuge Y, Arakawa M, Ishige K, Ito Y (2008) Distinct mechanism of cell death is responsible for tunicamycin-induced ER stress in SK-N-SH and SH-SY5Y cells. Neurosci Res 60:29–39. https://doi.org/10.1016/j.neures.2007.09.005
doi: 10.1016/j.neures.2007.09.005
pubmed: 18029041
Renton AE, Majounie E, Waite A, Simón-Sánchez J, Rollinson S, Gibbs JR et al (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72:257–268. https://doi.org/10.1016/j.neuron.2011.09.010
doi: 10.1016/j.neuron.2011.09.010
pubmed: 21944779
pmcid: 3200438
Rowland AA, Voeltz GK (2012) Endoplasmic reticulum-mitochondria contacts: function of the junction. Nat Rev Mol Cell Biol 13:607–625. https://doi.org/10.1038/nrm3440
doi: 10.1038/nrm3440
pubmed: 22992592
pmcid: 5111635
Saxena S, Cabuy E, Caroni P (2009) A role for motoneuron subtype–selective ER stress in disease manifestations of FALS mice. Nat Neurosci 12:627–636. https://doi.org/10.1038/nn.2297
doi: 10.1038/nn.2297
pubmed: 19330001
Schmitz A, Pinheiro Marques J, Oertig I, Maharjan N, Saxena S (2021) Emerging perspectives on dipeptide repeat proteins in C9ORF72 ALS/FTD. Front Cell Neurosci. https://doi.org/10.3389/fncel.2021.637548
doi: 10.3389/fncel.2021.637548
pubmed: 35173582
pmcid: 8377254
Singh R, Bartok A, Paillard M, Tyburski A, Elliott M, Hajnóczky G (2022) Uncontrolled mitchondrial calcium uptake underlies the pathogenesis of neurodegeneration in MICU1-deficient mice and patients. Sci Adv 8(11):eabj4716. https://doi.org/10.1126/sciadv.abj4716
doi: 10.1126/sciadv.abj4716
pubmed: 35302860
pmcid: 8932652
Soman SK, Bazała M, Keatinge M, Bandmann O, Kuznicki J (2019) Restriction of mitochondrial calcium overload by mcu inactivation renders neuroprotective effect in Zebrafish models of Parkinson’s disease. Biol Open. https://doi.org/10.1242/bio.044347
doi: 10.1242/bio.044347
pubmed: 31548178
pmcid: 6826286
Stucki DM, Ruegsegger C, Steiner S, Radecke J, Murphy MP, Zuber B et al (2016) Mitochondrial impairments contribute to Spinocerebellar ataxia type 1 progression and can be ameliorated by the mitochondria-targeted antioxidant MitoQ. Free Radic Biol Med 97:427–440. https://doi.org/10.1016/j.freeradbiomed.2016.07.005
doi: 10.1016/j.freeradbiomed.2016.07.005
pubmed: 27394174
Szabadkai G, Bianchi K, Várnai P, de Stefani D, Wieckowski MR, Cavagna D et al (2006) Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. JCB 175:901–911. https://doi.org/10.1083/jcb.200608073
doi: 10.1083/jcb.200608073
pubmed: 17178908
pmcid: 2064700
Takazawa T, Croft GF, Amoroso MW, Studer L, Wichterle H, Macdermott AB (2012) Maturation of spinal motor neurons derived from human embryonic stem cells. PLoS ONE 7:e40154. https://doi.org/10.1371/journal.pone.0040154
doi: 10.1371/journal.pone.0040154
pubmed: 22802953
pmcid: 3388990
Yamoah A, Tripathi P, Sechi A, Köhler C, Guo H, Chandrasekar A et al (2020) Aggregates of RNA binding proteins and ER chaperones linked to exosomes in granulovacuolar degeneration of the Alzheimer’s disease brain. J Alzheimers Dis 75:139–156. https://doi.org/10.3233/JAD-190722
doi: 10.3233/JAD-190722
pubmed: 32250292
Yu H, Lu S, Gasior K, Singh D, Vazquez-Sanchez S, Tapia O et al (2021) HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells. Science 371(6529):eabb4309. https://doi.org/10.1126/science.abb4309
doi: 10.1126/science.abb4309
pubmed: 33335017
Zhang K, Wang A, Zhong K, Qi S, Wei C, Shu X et al (2021) UBQLN2-HSP70 axis reduces poly-Gly-Ala aggregates and alleviates behavioral defects in the C9ORF72 animal model. Neuron 109:1949-1962.e6. https://doi.org/10.1016/j.neuron.2021.04.023
doi: 10.1016/j.neuron.2021.04.023
pubmed: 33991504
Zhang Y-J, Gendron TF, Grima JC, Sasaguri H, Jansen-West K, Xu Y-F et al (2016) C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins. Nat Neurosci 19:668–677. https://doi.org/10.1038/nn.4272
doi: 10.1038/nn.4272
pubmed: 26998601
pmcid: 5138863
Zhang Y-J, Jansen-West K, Xu Y-F, Gendron TF, Bieniek KF, Lin W-L et al (2014) Aggregation-prone c9FTD/ALS poly(GA) RAN-translated proteins cause neurotoxicity by inducing ER stress. Acta Neuropathol 128:505–524. https://doi.org/10.1007/s00401-014-1336-5
doi: 10.1007/s00401-014-1336-5
pubmed: 25173361
pmcid: 4159567