{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:00:34Z","timestamp":1790895634789,"version":"4.1.0"},"reference-count":181,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,11]],"date-time":"2020-04-11T00:00:00Z","timestamp":1586563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>The accumulation of abnormal protein aggregates represents a universal hallmark of neurodegenerative diseases (NDDs). Post-translational modifications (PTMs) regulate protein structure and function. Dysregulated PTMs may influence the propensity for protein aggregation in NDD-proteinopathies. To investigate this, we systematically reviewed the literature to evaluate effects of PTMs on aggregation propensity for major proteins linked to the pathogenesis and\/or progression of NDDs. A search of PubMed, MEDLINE, EMBASE, and Web of Science Core Collection was conducted to retrieve studies that investigated an association between PTMs and protein aggregation in seven NDDs: Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), Huntington\u2019s disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxias, transmissible spongiform encephalopathy, and multiple sclerosis. Together, 1222 studies were identified, of which 69 met eligibility criteria. We identified that the following PTMs, in isolation or combination, potentially act as modulators of proteinopathy in NDDs: isoaspartate formation in A\u03b2, phosphorylation of A\u03b2 or tau in AD; acetylation, 4-hydroxy-2-neonal modification, O-GlcNAcylation or phosphorylation of \u03b1-synuclein in PD; acetylation or phosphorylation of TAR DNA-binding protein-43 in ALS, and SUMOylation of superoxide dismutase-1 in ALS; and phosphorylation of huntingtin in HD. The potential pharmacological manipulation of these aggregation-modulating PTMs represents an as-yet untapped source of therapy to treat NDDs. <\/jats:p>","DOI":"10.3390\/brainsci10040232","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T04:45:31Z","timestamp":1586753131000},"page":"232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":156,"title":["Do Post-Translational Modifications Influence Protein Aggregation in Neurodegenerative Diseases: A Systematic Review"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6485-0045","authenticated-orcid":false,"given":"Larissa-Nele","family":"Schaffert","sequence":"first","affiliation":[{"name":"School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Uttoxeter Road, Derby DE22 3DT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1475-2476","authenticated-orcid":false,"given":"Wayne G.","family":"Carter","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Uttoxeter Road, Derby DE22 3DT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a033118","DOI":"10.1101\/cshperspect.a033118","article-title":"Clinical Neurology and epidemiology of the major neurodegenerative diseases","volume":"10","author":"Erkkinen","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a028035","DOI":"10.1101\/cshperspect.a028035","article-title":"Pathology of neurodegenerative diseases","volume":"9","author":"Dugger","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wolfe, M.S. (2018). Solving the puzzle of neurodegeneration. The Molecular and Cellular Basis of Neurodegenerative Diseases: Underlying Mechanisms, Elsevier.","DOI":"10.1016\/B978-0-12-811304-2.00001-8"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/s00415-018-9076-4","article-title":"Spinocerebellar ataxia: An update","volume":"266","author":"Sullivan","year":"2019","journal-title":"J. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hussain, R., Zubair, H., Pursell, S., and Shahab, M. (2018). Neurodegenerative diseases: Regenerative mechanisms and novel therapeutic approaches. Brain Sci., 8.","DOI":"10.3390\/brainsci8090177"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1038\/nm1066","article-title":"Protein aggregation and neurodegenerative disease","volume":"10","author":"Ross","year":"2004","journal-title":"Nat. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"290","DOI":"10.3389\/fncel.2018.00290","article-title":"Roles of post-translational modifications in spinocerebellar ataxias","volume":"12","author":"Wan","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3389\/fneur.2014.00251","article-title":"Detection of protein aggregates in brain and cerebrospinal fluid derived from multiple sclerosis patients","volume":"5","author":"David","year":"2014","journal-title":"Front. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/ene.13439","article-title":"Alzheimer\u2019s disease","volume":"25","author":"Lane","year":"2018","journal-title":"Eur. J. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s00401-013-1125-6","article-title":"Protein aggregation in amyotrophic lateral sclerosis","volume":"125","author":"Blokhuis","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/jnc.13772","article-title":"Pathogenic mechanisms of prion protein, amyloid-\u03b2 and \u03b1-synuclein misfolding: The prion concept and neurotoxicity of protein oligomers","volume":"139","author":"Ugalde","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/s41593-019-0385-4","article-title":"Bassoon proteinopathy drives neurodegeneration in multiple sclerosis","volume":"22","author":"Schattling","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/glia.440150206","article-title":"Amyloid precursor protein (APP) expression in multiple sclerosis lesions","volume":"15","author":"Gehrmann","year":"1995","journal-title":"Glia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"Rev-1781","DOI":"10.12688\/f1000research.15788.1","article-title":"Recent advances in understanding dominant spinocerebellar ataxias from clinical and genetic points of view","volume":"7","author":"Coarelli","year":"2018","journal-title":"F1000Res"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1097\/01.jnen.0000173890.79058.1d","article-title":"Visualization of newly deposited tau in neurofibrillary tangles and neuropil threads","volume":"64","author":"Miyasaka","year":"2005","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"743","DOI":"10.3389\/fnins.2017.00743","article-title":"DnaJ\/Hsp40 family and parkinson\u2019s disease","volume":"11","author":"Hasegawa","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_17","first-page":"309","article-title":"Genetics of neurodegenerative diseases: An overview","volume":"145","author":"Wiethoff","year":"2017","journal-title":"Handb. Clin. Neurol."},{"key":"ref_18","first-page":"723782","article-title":"Neuron Loss in Transgenic Mouse Models of Alzheimer\u2019s Disease","volume":"12","author":"Wirths","year":"2010","journal-title":"Int. J. Alzheimers Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1136\/jnnp.62.5.535","article-title":"Maternal transmission in sporadic Huntington\u2019s disease","volume":"62","author":"Rosich","year":"1997","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_20","unstructured":"Sim, V. (2018). Prion disease. BMJ Best Practice, BMJ Publishing Group. Available online: https:\/\/bestpractice.bmj.com\/topics\/en-gb\/484\/pdf\/484.pdf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.msard.2019.04.012","article-title":"Familial multiple sclerosis patients have a shorter delay in diagnosis than sporadic cases","volume":"32","author":"Steenhof","year":"2019","journal-title":"Mult. Scler. Relat. Discord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1017\/S0317167100004431","article-title":"Adult onset spinocerebellar ataxia in a Canadian movement disorders clinic","volume":"32","author":"Kraft","year":"2005","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s40249-016-0143-8","article-title":"Epidemiological characteristics of human prion diseases","volume":"5","author":"Chen","year":"2016","journal-title":"Infect. Dis. Poverty"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3389\/fncel.2013.00037","article-title":"Characterization of forebrain neurons derived from late-onset Huntington\u2019s disease human embryonic stem cell lines","volume":"7","author":"Niclis","year":"2013","journal-title":"Front. Cell. Neurosci."},{"key":"ref_25","unstructured":"GBD 2016 Motor Neuron Disease Collaborators (2018). Global, regional, and national burden of motor neuron diseases 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol., 17, 1083\u20131097."},{"key":"ref_26","unstructured":"GBD 2016 Multiple Sclerosis Collaborators (2019). Global, regional, and national burden of multiple sclerosis 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol., 18, 269\u2013285."},{"key":"ref_27","unstructured":"GBD 2016 Dementia Collaborators (2019). Global, regional, and national burden of Alzheimer\u2019s disease and other dementias, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol., 18, 88\u2013106."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s00702-017-1686-y","article-title":"Epidemiology of Parkinson\u2019s disease","volume":"124","author":"Tysnes","year":"2017","journal-title":"J. Neural. Transm."},{"key":"ref_29","first-page":"699","article-title":"The synaptic function of \u03b1-Synuclein","volume":"5","year":"2015","journal-title":"J. Park. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2016). 2016 Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dement. J. Alzheimers Dis., 12, 459\u2013509.","DOI":"10.1016\/j.jalz.2016.03.001"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/alzrt143","article-title":"Dementia: A global health priority - highlights from an ADI and World Health Organization report","volume":"4","author":"Wortmann","year":"2012","journal-title":"Alzheimers Res. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"b158","DOI":"10.1136\/bmj.b158","article-title":"Alzheimer\u2019s disease","volume":"338","author":"Burns","year":"2009","journal-title":"BMJ"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"645","DOI":"10.3233\/JAD-160907","article-title":"Recent progress in Alzheimer\u2019s disease research, Part 3: Diagnosis and treatment","volume":"57","author":"Hane","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/msj.20157","article-title":"Neuropathology of Alzheimer\u2019s disease","volume":"77","author":"Perl","year":"2010","journal-title":"Mt. Sinai. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s13311-014-0313-y","article-title":"\u03b2-Amyloid peptides and amyloid plaques in Alzheimer\u2019s disease","volume":"12","author":"Gouras","year":"2015","journal-title":"Neurotherapeutics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3389\/fnagi.2018.00118","article-title":"The physiological roles of amyloid-\u03b2 peptide hint at new ways to treat Alzheimer\u2019s disease","volume":"10","author":"Brothers","year":"2018","journal-title":"Front. Ageing Nurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1113\/jphysiol.2006.111203","article-title":"Physiological roles for amyloid beta peptides","volume":"575","author":"Pearson","year":"2006","journal-title":"J. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"17342","DOI":"10.1073\/pnas.0506723102","article-title":"3D structure of Alzheimer\u2019s amyloid-beta (1\u201342) fibrils","volume":"102","author":"Ritter","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological stageing of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00401-017-1707-9","article-title":"Roles of tau protein in health and disease","volume":"133","author":"Guo","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Medina, M., Hern\u00e1ndez, F., and Avila, J. (2016). New features about tau function and dysfunction. Biomolecules, 6.","DOI":"10.3390\/biom6020021"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ejmech.2017.07.070","article-title":"Tau protein aggregation in Alzheimer\u2019s disease: An attractive target for the development of novel therapeutic agents","volume":"139","author":"Jouanne","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.arr.2014.01.004","article-title":"Ageing and Parkinson\u2019s disease: Why is advancing age the biggest risk factor?","volume":"14","author":"Reeve","year":"2014","journal-title":"Ageing Res. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1007\/BF00686528","article-title":"The number of nerve cells in the substantia nigra in paralysis agitans","volume":"5","author":"Pakkenberg","year":"1965","journal-title":"Acta Neuropathol."},{"key":"ref_45","first-page":"504","article-title":"Parkinson\u2019s disease and its management: Part 1: Disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis","volume":"40","author":"DeMaagd","year":"2015","journal-title":"P T"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"\u03b1-Synuclein in Lewy bodies","volume":"388","author":"Spillanti","year":"1997","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.tins.2010.09.004","article-title":"\u03b1-Synuclein and dopamine at the crossroads of Parkinson\u2019s disease","volume":"33","author":"Venda","year":"2010","journal-title":"Trends Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1750-1326-4-9","article-title":"alpha-Synuclein and neuronal cell death","volume":"4","author":"Cookson","year":"2009","journal-title":"Mol. Neurodegener."},{"key":"ref_49","first-page":"879","article-title":"Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson\u2019s disease and dementia with Lewy bodies","volume":"152","author":"Baba","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1016\/j.mayocp.2018.04.007","article-title":"Amyotrophic lateral sclerosis: An update for 2018","volume":"93","author":"Oskarsson","year":"2018","journal-title":"Mayo Clin. Proc."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"171","DOI":"10.4103\/2152-7806.169561","article-title":"A comprehensive review of amyotrophic lateral sclerosis","volume":"6","author":"Zarei","year":"2015","journal-title":"Surg. Neurol. Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1093\/brain\/awz078","article-title":"The debated toxic role of aggregated TDP-43 in amyotrophic lateral sclerosis: A resolution in sight?","volume":"142","author":"Hergesheimer","year":"2019","journal-title":"Brain"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3389\/fnmol.2019.00025","article-title":"Molecular mechanisms of TDP-43 misfolding and pathology in amyotrophic lateral sclerosis","volume":"12","author":"Prasad","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.bbrc.2006.10.093","article-title":"TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"351","author":"Arai","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1111\/nan.12148","article-title":"Loss of nuclear TDP-43 in amyotrophic lateral sclerosis (ALS) causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurones","volume":"40","author":"Highley","year":"2014","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.bbadis.2006.05.004","article-title":"Structure, folding, and misfolding of Cu,Zn superoxide dismutase in amyotrophic lateral sclerosis","volume":"1762","author":"Rakhit","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Pansarasa, O., Bordoni, M., Diamanti, L., Sproviero, D., Gagliardi, S., and Cereda, C. (2018). SOD1 in Amyotrophic Lateral Sclerosis: \u201cAmbivalent\u201d Behavior Connected to the Disease. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051345"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"8209","DOI":"10.1073\/pnas.1801109115","article-title":"Endoplasmic reticulum stress leads to accumulation of wild-type SOD1 aggregates associated with sporadic amyotrophic lateral sclerosis","volume":"115","author":"Medinas","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1602\/neurorx.1.2.255","article-title":"Huntington\u2019s disease genetics","volume":"1","author":"Myers","year":"2004","journal-title":"NeuroRx"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1126\/science.277.5334.1990","article-title":"Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain","volume":"277","author":"DiFiglia","year":"1997","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.3892\/etm.2016.3566","article-title":"Huntington\u2019s disease: Molecular basis of pathology and status of current therapeutic approaches","volume":"12","author":"Huang","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1750-1172-5-40","article-title":"Huntington\u2019s disease: A clinical review","volume":"5","author":"Roos","year":"2010","journal-title":"Orphanet J Rare Dis"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/0092-8674(95)90542-1","article-title":"Targeted disruption of the Huntington\u2019s disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes","volume":"81","author":"Nasir","year":"1995","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"9455","DOI":"10.1523\/JNEUROSCI.4699-13.2014","article-title":"Huntingtin is required for normal excitatory synapse development in cortical and striatal circuits","volume":"34","author":"McKinstry","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"a007476","DOI":"10.1101\/cshperspect.a007476","article-title":"Huntington\u2019s disease","volume":"3","author":"Finkbeiner","year":"2011","journal-title":"Cold Spring Harb Perspect Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"221","DOI":"10.4161\/pri.23807","article-title":"Beta conformation of polyglutamine track revealed by a crystal structure of Huntingtin N-terminal region with insertion of three histidine residues","volume":"7","author":"Kim","year":"2013","journal-title":"Prion"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.expneurol.2011.12.013","article-title":"Protein aggregates in Huntington\u2019s disease","volume":"238","author":"Arrasate","year":"2012","journal-title":"Exp. Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nature01301","article-title":"Pivotal role of oligomerization in expanded polyglutamine neurodegenerative disorders","volume":"421","author":"Mahlke","year":"2003","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0092-8674(00)80513-9","article-title":"Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation","volume":"90","author":"Davies","year":"1997","journal-title":"Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"148","DOI":"10.4103\/0971-5916.155537","article-title":"An understanding of spinocerebellar ataxia","volume":"141","author":"Ramachandra","year":"2015","journal-title":"Indian J. Med. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/WNO0b013e3181b416de","article-title":"The spinocerebellar ataxias","volume":"29","author":"Paulson","year":"2009","journal-title":"J. Neuroophthalmol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1212\/01.wnl.0000196440.00297.67","article-title":"First symptom in sporadic Creutzfeldt\u2013Jakob disease","volume":"66","author":"Rabinovici","year":"2006","journal-title":"Neurology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/BF00304476","article-title":"Ultrastructural features of spongiform encephalopathy transmitted to mice from three species of bovidae","volume":"84","author":"Jeffrey","year":"1992","journal-title":"Acta Neuropathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.mpaic.2013.05.018","article-title":"Prion diseases","volume":"14","author":"Gupta","year":"2013","journal-title":"Anaesth. Inten. Care Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1093\/brain\/awl159","article-title":"Determinants of diagnostic investigation sensitivities across the clinical spectrum of sporadic Creutzfeldt\u2013Jakob disease","volume":"129","author":"Collins","year":"2006","journal-title":"Brain"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/1097-0029(20000701)50:1<58::AID-JEMT9>3.0.CO;2-5","article-title":"Immunolocalization of the cellular prion protein in normal brain","volume":"50","author":"Moya","year":"2000","journal-title":"Microsc. Res. Tech."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1038\/nn.3178","article-title":"Alzheimer amyloid-\u03b2 oligomer bound to postsynaptic prion protein activates Fyn to impair neurons","volume":"15","author":"Um","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3875","DOI":"10.3390\/v6103875","article-title":"The structure of human prions: From biology to structural models-considerations and pitfalls","volume":"6","author":"Wille","year":"2014","journal-title":"Viruses"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/356577a0","article-title":"Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein","volume":"356","author":"Bueler","year":"1992","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1016\/j.bbamem.2018.02.031","article-title":"Mechanism of aggregation and membrane interactions of mammalian prion protein","volume":"1860","author":"Mathew","year":"2018","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"10962","DOI":"10.1073\/pnas.90.23.10962","article-title":"Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins","volume":"90","author":"Pan","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"976","DOI":"10.3390\/ijms10030976","article-title":"Molecular pathology of human prion diseases","volume":"10","author":"Kovacs","year":"2009","journal-title":"Int. J. Mol. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-5793(97)00310-4","article-title":"Autocatalytic processes in cooperative mechanisms of prion diseases","volume":"407","author":"Laurent","year":"1997","journal-title":"FEBS Lett."},{"key":"ref_84","first-page":"1","article-title":"Multiple sclerosis: Pathogenesis, symptoms, diagnoses and cell-based therapy","volume":"19","author":"Ghasemi","year":"2017","journal-title":"Cell J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1097\/WCO.0000000000000094","article-title":"Relapsing and progressive forms of multiple sclerosis: Insights from pathology","volume":"27","author":"Dutta","year":"2014","journal-title":"Curr. Opin. Neurol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/S0896-6273(03)00088-6","article-title":"Functional inactivation of a fraction of excitatory synapses in mice deficient for the active zone protein bassoon","volume":"37","author":"Altrock","year":"2003","journal-title":"Neuron"},{"key":"ref_87","first-page":"1","article-title":"Protein aggregation and degradation mechanisms in neurodegenerative diseases","volume":"2","author":"Takalo","year":"2013","journal-title":"Am. J. Neurodegener. Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.devcel.2015.02.002","article-title":"Neuronal aggregates: Formation, clearance, and spreading","volume":"32","author":"Lim","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_89","unstructured":"(2020, March 15). Uniprot Modified Residues in Proteins. Available online: http:\/\/www.uniprot.org\/docs\/ptmlist.txt."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.gpb.2018.06.004","article-title":"PTMD: A database of human disease-associated Post-translational Modifications","volume":"16","author":"Xu","year":"2018","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6963","DOI":"10.1523\/JNEUROSCI.6513-10.2011","article-title":"Enhanced phosphatase activity attenuates \u03b1-synucleinopathy in a mouse model","volume":"31","author":"Lee","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1021\/acscentsci.9b00467","article-title":"Enhancement of the anti-aggregation activity of a molecular chaperone using a rationally designed post-translational modification","volume":"5","author":"Lindstedt","year":"2019","journal-title":"ACS Cent. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"160696","DOI":"10.1098\/rsos.160696","article-title":"Thioflavin T as an amyloid dye: Fibril quantification, optimal concentration and effect on aggregation","volume":"4","author":"Xue","year":"2017","journal-title":"R. Soc. Open Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"b2535","DOI":"10.1136\/bmj.b2535","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement","volume":"339","author":"Moher","year":"2009","journal-title":"BMJ"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1042\/BJ20130652","article-title":"Differential contribution of isoaspartate post-translational modifications to the fibrillization and toxic properties of amyloid \u03b2 and the Asn23 Iowa mutation","volume":"456","author":"Fossati","year":"2013","journal-title":"Biochem. J."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/jnr.10350","article-title":"Isoaspartate formation at position 23 of amyloid beta peptide enhanced fibril formation and deposited onto senile plaques and vascular amyloids in Alzheimer\u2019s disease","volume":"70","author":"Shimizu","year":"2002","journal-title":"J. Neurosci. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"12393","DOI":"10.1021\/bi0612667","article-title":"On the Seeding and Oligomerization of pGlu-Amyloid Peptides (in vitro)","volume":"45","author":"Schilling","year":"2006","journal-title":"Biochemistry"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1039\/C7MB00249A","article-title":"Phosphorylation of a full length amyloid-\u03b2 peptide modulates its amyloid aggregation, cell binding and neurotoxic properties","volume":"13","author":"Jamasbi","year":"2017","journal-title":"Mol. Biosyst."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1038\/emboj.2011.138","article-title":"Extracellular phosphorylation of the amyloid \u03b2-peptide promotes formation of toxic aggregates during the pathogenesis of Alzheimer\u2019s disease","volume":"30","author":"Kumar","year":"2011","journal-title":"EMBO J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s00401-016-1546-0","article-title":"Phosphorylation of the amyloid \u03b2-peptide at Ser26 stabilizes oligomeric assembly and increases neurotoxicity","volume":"131","author":"Kumar","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.febslet.2011.12.018","article-title":"Effect of N-homocysteinylation on physicochemical and cytotoxic properties of amyloid \u03b2-peptide","volume":"586","author":"Khodadadi","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1021\/tx500353s","article-title":"Nitration of Y10 in A\u03b21\u201340: Is it a compensatory reaction against oxidative\/nitrative stress and A\u03b2 aggregation?","volume":"28","author":"Zhao","year":"2015","journal-title":"Chem. Res. Toxicol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"11693","DOI":"10.1523\/JNEUROSCI.1081-16.2016","article-title":"Amyloid-\u03b2 peptide nitrotyrosination stabilizes oligomers and enhances NMDAR-Mediated Toxicity","volume":"36","author":"Guivernau","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.neuron.2011.07.001","article-title":"Nitration of tyrosine 10 critically enhances amyloid \u03b2 aggregation and plaque formation","volume":"71","author":"Hermes","year":"2011","journal-title":"Neuron"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"13100","DOI":"10.1074\/jbc.RA118.002275","article-title":"Glycation affects fibril formation of A\u03b2 peptides","volume":"293","author":"Emendato","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"44102","DOI":"10.1038\/srep44102","article-title":"A dual pathogenic mechanism links tau acetylation to sporadic tauopathy","volume":"7","author":"Trzeciakiewicz","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"6611","DOI":"10.1021\/jacs.8b02668","article-title":"Protein semisynthesis provides access to tau disease-associated post-translational modifications (PTMs) and paves the way to deciphering the tau ptm code in health and diseased states","volume":"140","author":"Lashuel","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/ncomms1255","article-title":"The acetylation of tau inhibits its function and promotes pathological tau aggregation","volume":"2","author":"Cohen","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Ferreon, J.C., Jain, A., Choi, K.J., Tsoi, P.S., MacKenzie, K.R., Jung, S.Y., and Ferreon, A.C. (2018). Acetylation disfavors tau phase separation. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051360"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1021\/bi500006v","article-title":"Nuclear magnetic resonance analysis of the acetylation pattern of the neuronal tau protein","volume":"53","author":"Kamah","year":"2014","journal-title":"Biochemistry"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"15277","DOI":"10.1074\/jbc.M117.794602","article-title":"An acetylation-phosphorylation switch that regulates tau aggregation propensity and function","volume":"292","author":"Carlomagno","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2590","DOI":"10.1016\/j.bbagen.2018.07.030","article-title":"Carbamylation promotes amyloidogenesis and induces structural changes in Tau-core hexapeptide fibrils","volume":"1862","author":"Baweja","year":"2018","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.febslet.2005.11.077","article-title":"C-terminal truncation modulates both nucleation and extension phases of \u03c4 fibrillization","volume":"580","author":"Yin","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.bbadis.2015.12.002","article-title":"Glycation alter the process of Tau phosphorylation to change Tau isoforms aggregation property","volume":"1862","author":"Liu","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.3233\/JAD-150960","article-title":"Halting of caspase activity protects tau from MC1-Conformational change and aggregation","volume":"54","author":"Mead","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"49694","DOI":"10.1074\/jbc.M405527200","article-title":"Pseudophosphorylation and glycation of tau protein enhance but do not trigger fibrillization in vitro","volume":"279","author":"Necula","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.bbapap.2010.10.005","article-title":"Pseudophosphorylation of tau protein directly modulates its aggregation kinetics","volume":"1814","author":"Chang","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"16586","DOI":"10.1073\/pnas.1417548111","article-title":"SUMOylation at K340 inhibits tau degradation through deregulating its phosphorylation and ubiquitination","volume":"111","author":"Luo","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/j.jmb.2014.01.004","article-title":"O-GlcNAc modification of tau directly inhibits its aggregation without perturbing the conformational properties of tau monomers","volume":"426","author":"Yuzwa","year":"2014","journal-title":"J. Mol. Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"22714","DOI":"10.1074\/jbc.M116.734350","article-title":"Modification of Tau by 8-Nitroguanosine 3\u2019,5\u2019-Cyclic Monophosphate (8-Nitro-cGMP): Effects of nitric oxide-linked chemical modification on tau aggregation","volume":"291","author":"Yoshitake","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1042\/BJ20140372","article-title":"Lysine methylation is an endogenous post-translational modification of tau protein in human brain and a modulator of aggregation propensity","volume":"462","author":"Funk","year":"2014","journal-title":"Biochem. J."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"13997","DOI":"10.1021\/bi051028w","article-title":"Site-Specific nitration differentially influences \u03c4 assembly in vitro","volume":"44","author":"Reynolds","year":"2005","journal-title":"Biochemistry"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Bartels, T., Kim, N.C., Luth, E.S., and Selkoe, D.J. (2014). N-alpha-acetylation of \u03b1-synuclein increases its helical folding propensity, GM1 binding specificity and resistance to aggregation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103727"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1002\/pro.2088","article-title":"N-terminal acetylation of \u03b1-synuclein induces increased transient helical propensity and decreased aggregation rates in the intrinsically disordered monomer","volume":"21","author":"Kang","year":"2012","journal-title":"Protein Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1021\/acschemneuro.7b00250","article-title":"N-Terminal Acetylation Preserves \u03b1-Synuclein from Oligomerization by Blocking Intermolecular Hydrogen Bonds","volume":"8","author":"Bu","year":"2017","journal-title":"ACS Chem. Neurosci."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"de Oliveira, R.M., Vicente, M.H., Francelle, L., Pinho, R., Szeg\u00f6, \u00c9.M., Martinho, R., Munari, F., L\u00e1zaro, D.F., Moniot, S., and Guerreiro, P. (2017). The mechanism of sirtuin 2-mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease. PLoS Biol., 15.","DOI":"10.1371\/journal.pbio.2000374"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Birol, M., Wojcik, S.P., Miranker, A.D., and Rhoades, E. (2019). Identification of N-linked glycans as specific mediators of neuronal uptake of acetylated \u03b1-Synuclein. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000318"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1016\/j.jmb.2019.04.026","article-title":"Alpha-Synuclein is a target of fic-mediated adenylylation\/ampylation: Possible implications for parkinson\u2019s disease","volume":"431","author":"Sanyal","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1093\/brain\/awx056","article-title":"Glycation potentiates alpha-synuclein-associated neurodegeneration in synucleinopathies","volume":"140","author":"Vicente","year":"2017","journal-title":"Brain"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1083\/jcb.201010117","article-title":"Sumoylation inhibits alpha-synuclein aggregation and toxicity","volume":"194","author":"Krumova","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.mcn.2013.01.004","article-title":"Oxidative stress-induced posttranslational modifications of alpha-synuclein: Specific modification of alpha-synuclein by 4-hydroxy-2-nonenal increases dopaminergic toxicity","volume":"54","author":"Xiang","year":"2013","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13024-015-0004-0","article-title":"Posttranslational modification and mutation of histidine 50 trigger alpha synuclein aggregation and toxicity","volume":"10","author":"Xiang","year":"2015","journal-title":"Mol. Neurodegener."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"5862","DOI":"10.1074\/jbc.M608126200","article-title":"Effect of 4-hydroxy-2-neonal modification on alpha-synuclein aggregation","volume":"282","author":"Qin","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1073\/pnas.1808845116","article-title":"\u03b1-Synuclein O-GlcNAcylation alters aggregation and toxicity, revealing certain residues as potential inhibitors of Parkinson\u2019s disease","volume":"116","author":"Levine","year":"2019","journal-title":"PNAS USA"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.neulet.2017.06.034","article-title":"Enzymatic O-GlcNAcylation of alpha-synuclein reduces aggregation and increases SDS-resistant soluble oligomers","volume":"655","author":"Zhang","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/nchem.2361","article-title":"O-GlcNAc modification blocks the aggregation and toxicity of the protein \u03b1-synuclein associated with Parkinson\u2019s disease","volume":"7","author":"Marotta","year":"2015","journal-title":"Nat. Chem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/ncb748","article-title":"\u03b1-Synuclein is phosphorylated in synucleinopathy lesions","volume":"4","author":"Fujiwara","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"4374","DOI":"10.1074\/jbc.M115.705095","article-title":"Effects of Serine 129 Phosphorylation on \u03b1-Synuclein Aggregation, Membrane Association, and Internalization","volume":"291","author":"Samuel","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"5041","DOI":"10.1021\/ja5131726","article-title":"Elucidating the role of site-specific nitration of \u03b1-synuclein in the pathogenesis of parkinson\u2019s disease via protein semisynthesis and mutagenesis","volume":"137","author":"Burai","year":"2015","journal-title":"J. Am. Chem. Soc."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1093\/jmcb\/mjr011","article-title":"A novel molecular mechanism for nitrated {alpha}-synuclein-induced cell death","volume":"3","author":"Liu","year":"2011","journal-title":"J. Mol. Cell. Biol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"47746","DOI":"10.1074\/jbc.M408906200","article-title":"Functional consequences of alpha-synuclein tyrosine nitration: Diminished binding to lipid vesicles and increased fibril formation","volume":"279","author":"Hodara","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"18344","DOI":"10.1074\/jbc.M000206200","article-title":"Dityrosine cross-linking promotes formation of stable alpha -synuclein polymers. Implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies","volume":"275","author":"Souza","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41467-017-00088-4","article-title":"Acetylation-induced TDP-43 pathology is suppressed by an HSF1-dependent chaperone program","volume":"8","author":"Wang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"5845","DOI":"10.1038\/ncomms6845","article-title":"An acetylation switch controls TDP-43 function and aggregation propensity","volume":"6","author":"Cohen","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"7607","DOI":"10.1073\/pnas.0900688106","article-title":"Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity","volume":"106","author":"Zhang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Carlomagno, Y., Zhang, Y., Davis, M., Lin, W.L., Cook, C., Dunmore, J., Tay, W., Menkosky, K., Cao, X., and Petrucelli, L. (2014). Casein kinase II induced polymerization of soluble TDP-43 into filaments is inhibited by heat shock proteins. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090452"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/ana.21425","article-title":"Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"64","author":"Hasegawa","year":"2008","journal-title":"Ann. Neurol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/j.1471-4159.2010.07098.x","article-title":"Regulation of TDP-43 aggregation by phosphorylation and p62\/SQSTM1","volume":"116","author":"Brady","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Li, H.Y., Yeh, P.A., Chiu, H.C., Tang, C.Y., and Tu, B.P. (2011). Hyperphosphorylation as a defense mechanism to reduce TDP-43 aggregation. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023075"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.biochi.2018.05.003","article-title":"The amyloidogenicity of a C-terminal region of TDP-43 implicated in Amyotrophic Lateral Sclerosis can be affected by anions, acetylation and homodimerization","volume":"150","author":"Prasad","year":"2018","journal-title":"Biochimie"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Yang, C., Tan, W., Whittle, C., Qui, L., Cao, L., Akbarian, S., and Xu, Z. (2011). The C-terminal TDP-43 fragments have a high aggregation propensity and harm neurons by a dominant-negative mechanism. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015878"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"19366","DOI":"10.1074\/jbc.M117.805283","article-title":"Lysine acylation in superoxide dismutase-1 electrostatically inhibits formation of fibrils with prion-like seeding","volume":"292","author":"Rasouli","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Niikura, T., Kita, Y., and Abe, Y. (2014). SUMO3 modification accelerates the aggregation of ALS-linked SOD1 mutants. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101080"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.bbrc.2006.06.092","article-title":"SUMO-1 modification increases human SOD1 stability and aggregation","volume":"347","author":"Fei","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.bpj.2016.06.018","article-title":"Acetylation within the first 17 residues of huntingtin exon 1 alters aggregation and lipid binding","volume":"111","author":"Chaibva","year":"2016","journal-title":"Biophys. J."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"5202","DOI":"10.1002\/anie.201611750","article-title":"Mutant exon1 huntingtin aggregation is regulated by T3 phosphorylation-induced structural changes and crosstalk between T3 phosphorylation and acetylation at K6","volume":"56","author":"Chiki","year":"2017","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1002\/anie.201307510","article-title":"One-Pot semisynthesis of Exon 1 of the huntingtin protein: New tools for elucidating the role of posttranslational modifications in the pathogenesis of huntington\u2019s disease","volume":"53","author":"Ansaloni","year":"2014","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"E10809","DOI":"10.1073\/pnas.1705372114","article-title":"Phosphorylation of huntingtin at residue T3 is decreased in Huntington\u2019s disease and modulates mutant huntingtin protein conformation","volume":"114","author":"Cariulo","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"18540","DOI":"10.1074\/jbc.RA118.004621","article-title":"N-terminal Huntingtin (Htt) phosphorylation is a molecular switch regulating Htt aggregation, helical conformation, internalization, and nuclear targeting","volume":"293","author":"DeGuire","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.neuron.2009.11.020","article-title":"Serines 13 and 16 are critical determinants of full-length human mutant huntingtin induced disease pathogenesis in HD mice","volume":"64","author":"Gu","year":"2009","journal-title":"Neuron"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S1097-2765(02)00602-0","article-title":"Proteases acting on mutant huntingtin generate cleaved products that differentially build up cytoplasmic and nuclear inclusions","volume":"10","author":"Lunkes","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"3262","DOI":"10.1242\/jcs.045567","article-title":"Mimicking proteasomal release of polyglutamine peptides initiates aggregation and toxicity","volume":"122","author":"Raspe","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.bbrc.2010.01.122","article-title":"Oxidative stress-enhanced SUMOylation and aggregation of ataxin-1: Implication of JNK pathway","volume":"393","author":"Ryu","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1093\/hmg\/ddi472","article-title":"Proteolytic cleavage of polyglutamine-expanded ataxin-3 is critical for aggregation and sequestration of non-expanded ataxin-3","volume":"15","author":"Haacke","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.bbapap.2007.05.005","article-title":"Effects of post-translational modifications on prion protein aggregation and the propagation of scrapie-like characteristics in vitro","volume":"1774","author":"Dear","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"8743","DOI":"10.1523\/JNEUROSCI.2294-09.2009","article-title":"Phosphorylation of prion protein at serine 43 induces prion protein conformational change","volume":"29","author":"Giannopoulos","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40478-017-0505-x","article-title":"Pyroglutamate and Isoaspartate modified Amyloid-Beta in ageing and Alzheimer\u2019s disease","volume":"6","author":"Moro","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Vigneswara, V., Cass, S., Wayne, D., Bolt, E.L., Ray, D.E., and Carter, W.G. (2013). Molecular ageing of alpha- and Beta-synucleins: Protein damage and repair mechanisms. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061442"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"32619","DOI":"10.1074\/jbc.M605421200","article-title":"Proteomic identification of novel substrates of a protein isoaspartyl methyltransferase repair enzyme","volume":"281","author":"Vigneswara","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s40478-018-0557-6","article-title":"Phosphorylation of different tau sites during progression of Alzheimer\u2019s disease","volume":"6","author":"Neddens","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/s41582-018-0013-z","article-title":"Tau-targeting therapies for Alzheimer disease","volume":"14","author":"Congdon","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1093\/brain\/awv376","article-title":"Brain propagation of transduced alpha-synuclein involves non-fibrillar protein species and is enhanced in alpha-synuclein null mice","volume":"139","author":"Helwig","year":"2016","journal-title":"Brain"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"4194","DOI":"10.1073\/pnas.1100976108","article-title":"In vivo demonstration that alpha-synuclein oligomers are toxic","volume":"108","author":"Winner","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1093\/jnen\/62.6.644","article-title":"Accumulation of phosphorylated \u03b1-synuclein in aging human brain","volume":"62","author":"Saito","year":"2003","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1159\/000439254","article-title":"Inhibition of Pathogenic mutant SOD1 aggregation in cultured motor neuronal cells by prevention of its sumoylation on lysine 75","volume":"16","author":"Dangoumau","year":"2016","journal-title":"Neurodegener. Dis."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"E7081","DOI":"10.1073\/pnas.1801772115","article-title":"N6-Furfuryladenine is protective in Huntington\u2019s disease models by signaling huntingtin phosphorylation","volume":"115","author":"Bowie","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Herrera, F., Branco-Santos, J., and Outeiro, T. (2019). Threonine 3 regulates Serine 13\/16 phosphorylation in the huntingtin exon 1. Matters Sel.","DOI":"10.19185\/matters.201905000005"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"138","DOI":"10.4103\/0972-2327.144284","article-title":"Toxic species in amyloid disorders: Oligomers or mature fibrils","volume":"18","author":"Verma","year":"2015","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1042\/BJ20111924","article-title":"Toxic prefibrillar \u03b1-synuclein amyloid oligomers adopt a distinctive antiparallel \u03b2-sheet structure","volume":"443","author":"Sarroukh","year":"2012","journal-title":"Biochem. J."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1042\/BJ20090379","article-title":"Antiparallel beta-sheet: A signature structure of the oligomeric amyloid beta-peptide","volume":"421","author":"Cerf","year":"2009","journal-title":"Biochem. J."},{"key":"ref_181","first-page":"373","article-title":"Secondary structure of amyloid beta peptide correlates with neurotoxic activity in vitro","volume":"45","author":"Simmons","year":"1994","journal-title":"Mol. Pharmacol."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/10\/4\/232\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:08:46Z","timestamp":1760364526000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/10\/4\/232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,11]]},"references-count":181,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["brainsci10040232"],"URL":"https:\/\/doi.org\/10.3390\/brainsci10040232","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,11]]}}}