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Review

Do Post-Translational Modifications Influence Protein Aggregation in Neurodegenerative Diseases: A Systematic Review

School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Uttoxeter Road, Derby DE22 3DT, UK
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Author to whom correspondence should be addressed.
Brain Sci. 2020, 10(4), 232; https://doi.org/10.3390/brainsci10040232
Received: 18 March 2020 / Revised: 5 April 2020 / Accepted: 7 April 2020 / Published: 11 April 2020
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’s disease (AD), Parkinson’s disease (PD), Huntington’s 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 Aβ, phosphorylation of Aβ or tau in AD; acetylation, 4-hydroxy-2-neonal modification, O-GlcNAcylation or phosphorylation of α-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. View Full-Text
Keywords: neurodegenerative diseases; neurotoxicity; post-translational modifications; protein aggregates neurodegenerative diseases; neurotoxicity; post-translational modifications; protein aggregates
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MDPI and ACS Style

Schaffert, L.-N.; Carter, W.G. Do Post-Translational Modifications Influence Protein Aggregation in Neurodegenerative Diseases: A Systematic Review. Brain Sci. 2020, 10, 232. https://doi.org/10.3390/brainsci10040232

AMA Style

Schaffert L-N, Carter WG. Do Post-Translational Modifications Influence Protein Aggregation in Neurodegenerative Diseases: A Systematic Review. Brain Sciences. 2020; 10(4):232. https://doi.org/10.3390/brainsci10040232

Chicago/Turabian Style

Schaffert, Larissa-Nele, and Wayne G. Carter. 2020. "Do Post-Translational Modifications Influence Protein Aggregation in Neurodegenerative Diseases: A Systematic Review" Brain Sciences 10, no. 4: 232. https://doi.org/10.3390/brainsci10040232

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