Altered succinylation of mitochondrial proteins, APP and tau in Alzheimer's disease.

Alzheimer Disease / genetics Amino Acid Sequence Amyloid beta-Protein Precursor / genetics Animals Autopsy Brain / metabolism Case-Control Studies Disease Models, Animal Gene Expression Profiling Humans Mice Mice, Transgenic Mitochondria / genetics Mitochondrial Proteins / genetics Plaque, Amyloid / genetics Protein Aggregates Protein Processing, Post-Translational Proteolysis Proteome / genetics Succinic Acid / metabolism tau Proteins / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
10 01 2022
Historique:
received: 29 02 2020
accepted: 25 11 2021
entrez: 11 1 2022
pubmed: 12 1 2022
medline: 11 2 2022
Statut: epublish

Résumé

Abnormalities in brain glucose metabolism and accumulation of abnormal protein deposits called plaques and tangles are neuropathological hallmarks of Alzheimer's disease (AD), but their relationship to disease pathogenesis and to each other remains unclear. Here we show that succinylation, a metabolism-associated post-translational protein modification (PTM), provides a potential link between abnormal metabolism and AD pathology. We quantified the lysine succinylomes and proteomes from brains of individuals with AD, and healthy controls. In AD, succinylation of multiple mitochondrial proteins declined, and succinylation of small number of cytosolic proteins increased. The largest increases occurred at critical sites of amyloid precursor protein (APP) and microtubule-associated tau. We show that in vitro, succinylation of APP disrupted its normal proteolytic processing thereby promoting Aβ accumulation and plaque formation and that succinylation of tau promoted its aggregation to tangles and impaired microtubule assembly. In transgenic mouse models of AD, elevated succinylation associated with soluble and insoluble APP derivatives and tau. These findings indicate that a metabolism-linked PTM may be associated with AD.

Identifiants

DOI: 10.1038/s41467-021-27572-2 PMID: 35013160 PMC: PMC8748865
pubmed: 35013160
doi: 10.1038/s41467-021-27572-2
pii: 10.1038/s41467-021-27572-2
pmc: PMC8748865
doi:

Substances chimiques

APP protein, human 0
Amyloid beta-Protein Precursor 0
MAPT protein, human 0
Mitochondrial Proteins 0
Protein Aggregates 0
Proteome 0
tau Proteins 0
Succinic Acid AB6MNQ6J6L

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

159

Subventions

Organisme : NIA NIH HHS
ID : RF1 AG058469
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG022547
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG059319
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY026576
Pays : United States
Organisme : NIDA NIH HHS
ID : HHSN271201300031C
Pays : United States
Organisme : NIH HHS
ID : S10 OD016320
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG014930
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG018877
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG058469
Pays : United States
Organisme : NIA NIH HHS
ID : F31 AG069416
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG066493
Pays : United States
Organisme : NIA NIH HHS
ID : R37 AG019391
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY029796
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005138
Pays : United States
Organisme : NIH HHS
ID : S10 OD017992
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066514
Pays : United States

Informations de copyright

© 2022. The Author(s).

Références

Usui, K. et al. Site-specific modification of Alzheimer’s peptides by cholesterol oxidation products enhances aggregation energetics and neurotoxicity. Proc. Natl Acad. Sci. USA 106, 18563–18568 (2009).
pubmed: 19841277 pmcid: 2774025 doi: 10.1073/pnas.0804758106
Tjernberg, L. O. et al. Arrest of -amyloid fibril formation by a pentapeptide ligand. J. Biol. Chem. 271, 8545–8548 (1996).
pubmed: 8621479 doi: 10.1074/jbc.271.15.8545
Cohen, T. J. et al. The acetylation of tau inhibits its function and promotes pathological tau aggregation. Nat. Commun. 2, 252 (2011).
pubmed: 21427723 doi: 10.1038/ncomms1255
Gordon, B. A. et al. Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer’s disease: a longitudinal study. Lancet Neurol. 17, 241–250 (2018).
pubmed: 29397305 pmcid: 5816717 doi: 10.1016/S1474-4422(18)30028-0
Dumont, M. et al. Mitochondrial dihydrolipoyl succinyltransferase deficiency accelerates amyloid pathology and memory deficit in a transgenic mouse model of amyloid deposition. Free Radic. Biol. Med. 47, 1019–1027 (2009).
pubmed: 19596066 pmcid: 2761144 doi: 10.1016/j.freeradbiomed.2009.07.008
Blass, J. P., Baker, A. C., Ko, L. & Black, R. S. Induction of alzheimer antigens by an uncoupler of oxidative phosphorylation. Arch. Neurol. 47, 864–869 (1990).
pubmed: 2375692 doi: 10.1001/archneur.1990.00530080046009
Cheng, B. & Mattson, M. P. Glucose deprivation elicits neurofibrillary tangle-like antigenic changes in hippocampal neurons: prevention by NGF and bFGF. Exp. Neurol. 117, 114–123 (1992).
pubmed: 1323483 doi: 10.1016/0014-4886(92)90120-F
Caselli, R. J., Knopman, D. S. & Bu, G. An agnostic reevaluation of the amyloid cascade hypothesis of Alzheimer‘s disease pathogenesis: The role of APP homeostasis. Alzheimer‘s Dementia 16, 1582–1590 (2020).
pubmed: 32588983 doi: 10.1002/alz.12124
Sims, R., Hill, M. & Williams, J. The multiplex model of the genetics of Alzheimer’s disease. Nat. Neurosci. 23, 311–322 (2020).
pubmed: 32112059 doi: 10.1038/s41593-020-0599-5
Bramblett, G. T. et al. Abnormal tau phosphorylation at Ser396 in Alzheimer’s disease recapitulates development and contributes to reduced microtubule binding. Neuron 10, 1089–1099 (1993).
pubmed: 8318230 doi: 10.1016/0896-6273(93)90057-X
Min, S.-W. et al. Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron 67, 953–966 (2010).
pubmed: 20869593 pmcid: 3035103 doi: 10.1016/j.neuron.2010.08.044
Engstrom, A. K. et al. The inhibition of LSD1 via sequestration contributes to tau-mediated neurodegeneration. Proc. Natl. Acad. Sci. 117, 29133–29143 (2020).
pubmed: 33139560 pmcid: 7682552 doi: 10.1073/pnas.2013552117
Liu, F., Iqbal, K., Grundke-Iqbal, I., Hart, G. W. & Gong, C.-X. O-GlcNAcylation regulates phosphorylation of tau: a mechanism involved in Alzheimer’s disease. Proc. Natl Acad. Sci. USA 101, 10804 (2004).
pubmed: 15249677 pmcid: 490015 doi: 10.1073/pnas.0400348101
Fukushima, A. et al. Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart. Am. J. Physiol. Heart Circ. Physiol. 311, H347–H363 (2016).
pubmed: 27261364 doi: 10.1152/ajpheart.00900.2015
Nishida, Y. et al. SIRT5 regulates both cytosolic and mitochondrial protein malonylation with glycolysis as a major target. Mol. Cell 59, 321–332 (2015).
pubmed: 26073543 pmcid: 4571487 doi: 10.1016/j.molcel.2015.05.022
Mapstone, M. et al. Metabolic correlates of prevalent mild cognitive impairment and Alzheimer’s disease in adults with Down syndrome. Alzheimer’s Dement. 12, e12028 (2020).
Johnson, E. C. B. et al. Large-scale proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation. Nat. Med. 26, 769–780 (2020).
pubmed: 32284590 pmcid: 7405761 doi: 10.1038/s41591-020-0815-6
Arnold, M. et al. Sex and APOE ε4 genotype modify the Alzheimer’s disease serum metabolome. Nat. Commun. 11, 1148 (2020).
pubmed: 32123170 pmcid: 7052223 doi: 10.1038/s41467-020-14959-w
Swarup, V. et al. Identification of Conserved Proteomic Networks in Neurodegenerative Dementia. Cell Rep. 31, 107807 (2020).
pubmed: 32579933 pmcid: 8221021 doi: 10.1016/j.celrep.2020.107807
Mastrogiacomo, F., Bergeron, C. & Kish, S. J. Brain α-ketoglutarate dehydrotenase complex activity in Alzheimer’s disease. J. Neurochem. 61, 2007–2014 (1993).
pubmed: 8245957 doi: 10.1111/j.1471-4159.1993.tb07436.x
Gibson, G. E. et al. Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer’s disease. Arch. Neurol. 45, 836–840 (1988).
pubmed: 3395256 doi: 10.1001/archneur.1988.00520320022009
Weinert, B. T. et al. Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. Cell Rep. 4, 842–851 (2013).
pubmed: 23954790 doi: 10.1016/j.celrep.2013.07.024
Chen, H. et al. Mild metabolic perturbations alter succinylation of mitochondrial proteins. J. Neurosci. Res. 95, 2244–2252 (2017).
pubmed: 28631845 pmcid: 5597472 doi: 10.1002/jnr.24103
Yang, Y. & Gibson, G. E. Succinylation links metabolism to protein functions. Neurochem. Res. 44, 2346–2359 (2019).
pubmed: 30903449 pmcid: 6755074 doi: 10.1007/s11064-019-02780-x
Du, J. et al. Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science 334, 806 (2011).
pubmed: 22076378 pmcid: 3217313 doi: 10.1126/science.1207861
Pan, J., Chen, R., Li, C., Li, W. & Ye, Z. Global analysis of protein lysine succinylation profiles and their overlap with lysine acetylation in the marine bacterium Vibrio parahemolyticus. J. Proteome Res. 14, 4309–4318 (2015).
pubmed: 26369940 doi: 10.1021/acs.jproteome.5b00485
Xu, H. et al. Lysine acetylation and succinylation in HeLa cells and their essential roles in response to UV-induced stress. Sci. Rep. 6, 30212 (2016).
pubmed: 27452117 pmcid: 4959001 doi: 10.1038/srep30212
Colak, G. et al. Identification of lysine succinylation substrates and the succinylation regulatory enzyme CobB in Escherichia coli. Mol. Cell. Proteomics 12, 3509–3520 (2013).
pubmed: 24176774 pmcid: 3861704 doi: 10.1074/mcp.M113.031567
Park, J. et al. SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. Mol. Cell 50, 919–930 (2013).
pubmed: 23806337 pmcid: 3769971 doi: 10.1016/j.molcel.2013.06.001
Rardin, M. J. et al. SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks. Cell Metab. 18, 920–933 (2013).
pubmed: 24315375 pmcid: 4105152 doi: 10.1016/j.cmet.2013.11.013
Boada, M. et al. ATP5H/KCTD2 locus is associated with Alzheimer’s disease risk. Mol. Psychiatry 19, 682 (2013).
pubmed: 23857120 pmcid: 4031637 doi: 10.1038/mp.2013.86
Terni, B., Boada, J., Portero-Otin, M., Pamplona, R. & Ferrer, I. Mitochondrial ATP-synthase in the entorhinal cortex is a target of oxidative stress at stages I/II of Alzheimer’s disease pathology. Brain Pathol. 20, 222–233 (2010).
pubmed: 19298596 doi: 10.1111/j.1750-3639.2009.00266.x
Banerjee, K. et al. Mild mitochondrial metabolic deficits by α-ketoglutarate dehydrogenase inhibition cause prominent changes in intracellular autophagic signaling: Potential role in the pathobiology of Alzheimer’s disease. Neurochem. Int. 96, 32–45 (2016).
pubmed: 26923918 pmcid: 4860123 doi: 10.1016/j.neuint.2016.02.011
Gibson, G. E. et al. Alpha‐ketoglutarate dehydrogenase complex‐dependent succinylation of proteins in neurons and neuronal cell lines. J. Neurochem. 134, 86–96 (2015).
pubmed: 25772995 pmcid: 4472501 doi: 10.1111/jnc.13096
Wang, Y. et al. KAT2A coupled with the alpha-KGDH complex acts as a histone H3 succinyltransferase. Nature 552, 273–277 (2017).
pubmed: 29211711 pmcid: 5841452 doi: 10.1038/nature25003
Lambert, M. P. et al. Monoclonal antibodies that target pathological assemblies of Abeta. J. Neurochem. 100, 23–35 (2007).
pubmed: 17116235 doi: 10.1111/j.1471-4159.2006.04157.x
Kaden, D. et al. Novel APP/Aβ mutation K16N produces highly toxic heteromeric Aβ oligomers. EMBO Mol. Med. 4, 647–659 (2012).
pubmed: 22514144 pmcid: 3407951 doi: 10.1002/emmm.201200239
Seyfried, N. T. et al. A multi-network approach identifies protein-specific co-expression in asymptomatic and symptomatic Alzheimer’s disease. Cell Syst. 4, 60–72.e64 (2017).
pubmed: 27989508 doi: 10.1016/j.cels.2016.11.006
Sinha, S., Lopes, D. H. J. & Bitan, G. A key role for lysine residues in amyloid β-protein folding, assembly, and toxicity. ACS Chem. Neurosci. 3, 473–481 (2012).
pubmed: 22860216 pmcid: 3382451 doi: 10.1021/cn3000247
Cline, E. N., Bicca, M. A., Viola, K. L. & Klein, W. L. The amyloid-beta oligomer hypothesis: beginning of the third decade. J. Alzheimers Dis. 64, S567–S610 (2018).
pubmed: 29843241 pmcid: 6004937 doi: 10.3233/JAD-179941
Friedman, R. Aggregation of amyloids in a cellular context: modelling and experiment. Biochem. J. 438, 415–426 (2011).
pubmed: 21867485 doi: 10.1042/BJ20110369
Suh, J. et al. ADAM10 missense mutations potentiate β-amyloid accumulation by impairing prodomain chaperone function. Neuron 80, 385–401 (2013).
pubmed: 24055016 pmcid: 4105199 doi: 10.1016/j.neuron.2013.08.035
von Bergen, M. et al. Assembly of τ protein into Alzheimer paired helical filaments depends on a local sequence motif (306VQIVYK311) forming β structure. Proc. Natl Acad. Sci. USA 97, 5129–5134 (2000).
doi: 10.1073/pnas.97.10.5129
Goux, W. J. et al. The formation of straight and twisted filaments from short tau peptides. J. Biol. Chem. 279, 26868–26875 (2004).
pubmed: 15100221 doi: 10.1074/jbc.M402379200
Li, W. & Lee, V. M.-Y. Characterization of two VQIXXK motifs for tau fibrillization in vitro. Biochemistry 45, 15692–15701 (2006).
pubmed: 17176091 doi: 10.1021/bi061422+
Lasagna-Reeves, C. A. et al. Identification of oligomers at early stages of tau aggregation in Alzheimer’s disease. FASEB J. 26, 1946–1959 (2012).
pubmed: 22253473 pmcid: 4046102 doi: 10.1096/fj.11-199851
Li, W. & Lee, V. M. Y. Characterization of two VQIXXK motifs for tau fibrillization in vitro. Biochemistry 45, 15692–15701 (2006).
pubmed: 17176091 doi: 10.1021/bi061422+
von Bergen, M. et al. The core of tau-paired helical filaments studied by scanning transmission electron microscopy and limited proteolysis. Biochemistry 45, 6446–6457 (2006).
doi: 10.1021/bi052530j
Fitzpatrick, A. W. et al. Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature 547, 185 (2017).
pubmed: 28678775 pmcid: 5552202 doi: 10.1038/nature23002
Barghorn, S., Davies, P. & Mandelkow, E. Tau paired helical filaments from Alzheimer’s disease brain and assembled in vitro are based on β-structure in the core domain. Biochemistry 43, 1694–1703 (2004).
pubmed: 14769047 doi: 10.1021/bi0357006
Lu, P.-J., Wulf, G., Zhou, X. Z., Davies, P. & Lu, K. P. The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein. Nature 399, 784 (1999).
pubmed: 10391244 doi: 10.1038/21650
Gigant, B. et al. Mechanism of tau-promoted microtubule assembly as probed by NMR spectroscopy. J. Am. Chem. Soc. 136, 12615–12623 (2014).
pubmed: 25162583 doi: 10.1021/ja504864m
Kadavath, H. et al. Tau stabilizes microtubules by binding at the interface between tubulin heterodimers. Proc. Natl Acad. Sci. USA 112, 7501–7506 (2015).
pubmed: 26034266 pmcid: 4475932 doi: 10.1073/pnas.1504081112
Kellogg, E. H. et al. Near-atomic model of microtubule-tau interactions. Science 360, 1242–1246 (2018).
pubmed: 29748322 pmcid: 6225777 doi: 10.1126/science.aat1780
Kadavath, H. et al. Tau stabilizes microtubules by binding at the interface between tubulin heterodimers. Proc. Natl Acad. Sci. USA 112, 7501–7506 (2015).
pubmed: 26034266 pmcid: 4475932 doi: 10.1073/pnas.1504081112
Hong, L., Huang, H. C. & Jiang, Z. F. Relationship between amyloid-beta and the ubiquitin-proteasome system in Alzheimer’s disease. Neurol. Res. 36, 276–282 (2014).
pubmed: 24512022 doi: 10.1179/1743132813Y.0000000288
Bellia, F. et al. Ubiquitin binds the amyloid β peptide and interferes with its clearance pathways. Chem. Sci. 10, 2732–2742 (2019).
pubmed: 30996991 pmcid: 6419943 doi: 10.1039/C8SC03394C
Min, S.-W. et al. Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits. Nat. Med. 21, 1154 (2015).
pubmed: 26390242 pmcid: 4598295 doi: 10.1038/nm.3951
Carlomagno, Y. et al. An acetylation-phosphorylation switch that regulates tau aggregation propensity and function. J. Biol. Chem. 292, 15277–15286 (2017).
pubmed: 28760828 pmcid: 5602388 doi: 10.1074/jbc.M117.794602
Sutendra, G. et al. A nuclear pyruvate dehydrogenase complex is important for the generation of acetyl-CoA and histone acetylation. Cell 158, 84–97 (2014).
pubmed: 24995980 doi: 10.1016/j.cell.2014.04.046
Trushina, E. et al. Defects in mitochondrial dynamics and metabolomic signatures of evolving energetic stress in mouse models of familial Alzheimer’s disease. PLoS ONE 7, e32737 (2012).
pubmed: 22393443 pmcid: 3290628 doi: 10.1371/journal.pone.0032737
Pan, X. et al. Powerful beneficial effects of benfotiamine on cognitive impairment and β-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice. Brain 133, 1342–1351 (2010).
pubmed: 20385653 doi: 10.1093/brain/awq069
Tapias, V. et al. Benfotiamine treatment activates the Nrf2/ARE pathway and is neuroprotective in a transgenic mouse model of tauopathy. Hum. Mol. Genet. 27, 2874–2892 (2018).
pubmed: 29860433 pmcid: 6077804 doi: 10.1093/hmg/ddy201
Gibson, G. E. et al. Benfotiamine and cognitive decline in Alzheimer’s disease: results of a randomized placebo-controlled phase IIa clinical trial. J. Alzheimers Dis. 78, 989–1010 (2020).
pubmed: 33074237 pmcid: 7880246 doi: 10.3233/JAD-200896
Goedert, M. et al. in Frontotemporal Dementias: Emerging Milestones of the 21st Century (eds. Ghetti, B., Buratti, E., Boeve, B. & Rademakers, R.) 177–199 (Springer International Publishing, 2021).
Zhang, W. et al. Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer’s and Pick’s diseases. eLife 8, e43584 (2019).
pubmed: 30720432 pmcid: 6375701 doi: 10.7554/eLife.43584
Irwin, D. J. et al. Acetylated tau, a novel pathological signature in Alzheimer’s disease and other tauopathies. Brain 135, 807–818 (2012).
pubmed: 22366796 pmcid: 3286338 doi: 10.1093/brain/aws013
Morris, M. et al. Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice. Nat. Neurosci. 18, 1183–1189 (2015).
pubmed: 26192747 pmcid: 8049446 doi: 10.1038/nn.4067
Deutsch, E. W. et al. The ProteomeXchange consortium in 2017: supporting the cultural change in proteomics public data deposition. Nucleic Acids Res. 45, D1100–D1106 (2016).
pubmed: 27924013 pmcid: 5210636 doi: 10.1093/nar/gkw936
Perez-Riverol, Y. et al. PRIDE inspector toolsuite: moving toward a universal visualization tool for proteomics data standard formats and quality assessment of ProteomeXchange datasets. Mol. Cell. Proteomics 15, 305–317 (2016).
pubmed: 26545397 doi: 10.1074/mcp.O115.050229
Perez-Riverol, Y. et al. The PRIDE database and related tools and resources in 2019: improving support for quantification data. Nucleic Acids Res. 47, D442–D450 (2018).
pmcid: 6323896 doi: 10.1093/nar/gky1106
Yang, Y. et al. Evaluation of different multidimensional LC–MS/MS pipelines for isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of potato tubers in response to cold storage. J. Proteome Res. 10, 4647–4660 (2011).
pubmed: 21842911 doi: 10.1021/pr200455s
Chen, J.-W. et al. Proteomic comparison of historic and recently emerged hypervirulent Clostridium difficile strains. J. Proteome Res. 12, 1151–1161 (2013).
pubmed: 23298230 doi: 10.1021/pr3007528
Yang, S. et al. Parallel comparative proteomics and phosphoproteomics reveal that cattle myostatin regulates phosphorylation of key enzymes in glycogen metabolism and glycolysis pathway. Oncotarget 9, 11352 (2018).
pubmed: 29541418 pmcid: 5834288 doi: 10.18632/oncotarget.24250
Thomas, C. J., Cleland, T. P., Zhang, S., Gundberg, C. M. & Vashishth, D. Identification and characterization of glycation adducts on osteocalcin. Anal. Biochem. 525, 46–53 (2017).
pubmed: 28237256 pmcid: 5490980 doi: 10.1016/j.ab.2017.02.011
Hatai, J., Motiei, L. & Margulies, D. Analyzing amyloid beta aggregates with a combinatorial fluorescent molecular sensor. J. Am. Chem. Soc. 139, 2136–2139 (2017).
pubmed: 28170248 doi: 10.1021/jacs.6b10809
KrishnaKumar, V. G., Paul, A., Gazit, E. & Segal, D. Mechanistic insights into remodeled Tau-derived PHF6 peptide fibrils by Naphthoquinone-Tryptophan hybrids. Sci. Rep. 8, 71 (2018).
pubmed: 29311706 pmcid: 5758761 doi: 10.1038/s41598-017-18443-2
Frenkel-Pinter, M. et al. Naphthoquinone-tryptophan hybrid inhibits aggregation of the tau-derived peptide PHF6 and reduces neurotoxicity. J. Alzheimers Dis. 51, 165–178 (2016).
pubmed: 26836184 doi: 10.3233/JAD-150927
Eliezer, D. et al. Residual structure in the repeat domain of Tau: echoes of microtubule binding and paired helical filament formation. Biochemistry 44, 1026–1036 (2005).
pubmed: 15654759 doi: 10.1021/bi048953n
Eliezer, D. et al. Residual structure in the repeat domain of tau: echoes of microtubule binding and paired helical filament formation. Biochemistry 44, 1026–1036 (2005).
pubmed: 15654759 doi: 10.1021/bi048953n
Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–2504 (2003).
pubmed: 14597658 pmcid: 403769 doi: 10.1101/gr.1239303
Szklarczyk, D. et al. STRING v10: protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 43, D447–D452 (2014).
pubmed: 25352553 pmcid: 4383874 doi: 10.1093/nar/gku1003
Schwartz, D. & Gygi, S. P. An iterative statistical approach to the identification of protein phosphorylation motifs from large-scale data sets. Nat. Biotechnol. 23, 1391 (2005).
pubmed: 16273072 doi: 10.1038/nbt1146
Chou, M. F. & Schwartz, D. Biological sequence motif discovery using motif‐x. Curr. Protoc. Bioinformatics 35, 13.15. 11–13.15. 24 (2011).
Colaert, N., Helsens, K., Martens, L., Vandekerckhove, J. & Gevaert, K. Improved visualization of protein consensus sequences by iceLogo. Nat. Methods 6, 786 (2009).
pubmed: 19876014 doi: 10.1038/nmeth1109-786
Bindea, G. et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25, 1091–1093 (2009).
pubmed: 19237447 pmcid: 2666812 doi: 10.1093/bioinformatics/btp101
Tyanova, S. et al. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat. Methods 13, 731 (2016).
pubmed: 27348712 doi: 10.1038/nmeth.3901
De Hoon, M. J., Imoto, S., Nolan, J. & Miyano, S. Open source clustering software. Bioinformatics 20, 1453–1454 (2004).
pubmed: 14871861 doi: 10.1093/bioinformatics/bth078
Chishti, M. A. et al. Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695*. J. Biol. Chem. 276, 21562–21570 (2001).
pubmed: 11279122 doi: 10.1074/jbc.M100710200
Pennanen, L., Welzl, H., D’Adamo, P., Nitsch, R. M. & Götz, J. Accelerated extinction of conditioned taste aversion in P301L tau transgenic mice. Neurobiol. Dis. 15, 500–509 (2004).
pubmed: 15056457 doi: 10.1016/j.nbd.2003.11.020

Auteurs

Yun Yang (Y)

Integrated Medicine Research Center for Neurological Rehabilitation, College of Medicine, Jiaxing University, 314001, Jiaxing, China.
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10065, USA.
Burke Neurological Institute, White Plains, NY, 10605, USA.

Victor Tapias (V)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10065, USA.
ORCID: 0000-0002-1783-7320

Diana Acosta (D)

Department of Biochemistry, Weill Cornell Medicine, New York, NY, 10065, USA.
ORCID: 0000-0001-5902-913X

Hui Xu (H)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10065, USA.
Burke Neurological Institute, White Plains, NY, 10605, USA.
ORCID: 0000-0002-0434-1000

Huanlian Chen (H)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10065, USA.
Burke Neurological Institute, White Plains, NY, 10605, USA.

Ruchika Bhawal (R)

Proteomics and Metabolomics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY, 14853, USA.
ORCID: 0000-0002-5705-5032

Elizabeth T Anderson (ET)

Proteomics and Metabolomics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY, 14853, USA.

Elena Ivanova (E)

Imaging Core, Burke Neurological Institute, White Plains, NY, 10605, USA.
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 10591, USA.

Hening Lin (H)

Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA.
Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA.
ORCID: 0000-0002-0255-2701

Botir T Sagdullaev (BT)

Ophthalmology and Neuroscience, Weill Cornell Medicine, New York, NY, 10065, USA.
Laboratory for Visual Plasticity and Repair, Burke Neurological Institute, White Plains, NY, 10605, USA.
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 10591, USA.

Jianer Chen (J)

Integrated Medicine Research Center for Neurological Rehabilitation, College of Medicine, Jiaxing University, 314001, Jiaxing, China.
ORCID: 0000-0002-7101-208X

William L Klein (WL)

Department of Neurobiology, Northwestern University, Evanston, IL, 60208, USA.
ORCID: 0000-0002-3047-9978

Kirsten L Viola (KL)

Department of Neurobiology, Northwestern University, Evanston, IL, 60208, USA.
ORCID: 0000-0002-9862-6436

Sam Gandy (S)

Department of Neurology and Mount Sinai Center for Cognitive Health and NFL Neurological Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Research and Development Service and Division of Neurology, James J Peters VA Medical Center, 130 West Kingsbridge Rd, Bronx, NY, 10468, USA.
James J Peters Veterans Medical Center, Bronx, NY, 10468, USA.
Department of Psychiatry Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
ORCID: 0000-0001-6455-4721

Vahram Haroutunian (V)

Department of Psychiatry Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
JJ Peters VA Medical Center MIRECC, Bronx, NY, 10468, USA.
Mount Sinai NIH Neurobiobank, New York, NY, 10029, USA.
ORCID: 0000-0001-5860-2512

M Flint Beal (MF)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10065, USA.

David Eliezer (D)

Department of Biochemistry, Weill Cornell Medicine, New York, NY, 10065, USA.
ORCID: 0000-0002-1311-7537

Sheng Zhang (S)

Proteomics and Metabolomics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY, 14853, USA.
ORCID: 0000-0001-8206-1007

Gary E Gibson (GE)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10065, USA. ggibson@med.cornell.edu.
Burke Neurological Institute, White Plains, NY, 10605, USA. ggibson@med.cornell.edu.
ORCID: 0000-0003-2549-2876

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Classifications MeSH

questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Altered succinylation of mitochondrial...
questionsmedicales.fr › Sciences de l'information › Sources d'information › Services d'information › Documentation › Données de séquences moléculaires › Séquence d'acides aminés › Altered succinylation of mitochondrial...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines sécrétoires inhibitrices de protéinases › Protéase nexines › Précurseur de la protéine bêta-amyloïde › Altered succinylation of mitochondrial...
questionsmedicales.fr › Eucaryotes › Animaux › Altered succinylation of mitochondrial...
questionsmedicales.fr › Sciences sociales › Criminologie › Sciences légales › Médecine légale › Autopsie › Altered succinylation of mitochondrial...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Altered succinylation of mitochondrial...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › Altered succinylation of mitochondrial...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Altered succinylation of mitochondrial...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Altered succinylation of mitochondrial...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Altered succinylation of mitochondrial...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Altered succinylation of mitochondrial...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Altered succinylation of mitochondrial...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Mitochondries › Altered succinylation of mitochondrial...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines mitochondriales › Altered succinylation of mitochondrial...
questionsmedicales.fr › États, signes et symptômes pathologiques › États anatomopathologiques › Plaque amyloïde › Altered succinylation of mitochondrial...
questionsmedicales.fr › Structures macromoléculaires › Agrégats de protéines › Altered succinylation of mitochondrial...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Modification traductionnelle des protéines › Maturation post-traductionnelle des protéines › Altered succinylation of mitochondrial...
questionsmedicales.fr › Métabolisme › Protéolyse › Altered succinylation of mitochondrial...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéome › Altered succinylation of mitochondrial...
questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Acides acycliques › Diacides carboxyliques › Succinates › Acide succinique › Altered succinylation of mitochondrial...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Protéines tau › Altered succinylation of mitochondrial...