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Lookup NU author(s): Dr NELSON Manzanza, Lucy Sedlackova, Professor Raj KalariaORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© Copyright © 2021 Manzanza, Sedlackova and Kalaria. Lewy Body Disorders (LBDs) lie within the spectrum of age-related neurodegenerative diseases now frequently categorized as the synucleinopathies. LBDs are considered to be among the second most common form of neurodegenerative dementias after Alzheimer's disease. They are progressive conditions with variable clinical symptoms embodied within specific cognitive and behavioral disorders. There are currently no effective treatments for LBDs. LBDs are histopathologically characterized by the presence of abnormal neuronal inclusions commonly known as Lewy Bodies (LBs) and extracellular Lewy Neurites (LNs). The inclusions predominantly comprise aggregates of alpha-synuclein (aSyn). It has been proposed that post-translational modifications (PTMs) such as aSyn phosphorylation, ubiquitination SUMOylation, Nitration, o-GlcNacylation, and Truncation play important roles in the formation of toxic forms of the protein, which consequently facilitates the formation of these inclusions. This review focuses on the role of different PTMs in aSyn in the pathogenesis of LBDs. We highlight how these PTMs interact with aSyn to promote misfolding and aggregation and interplay with cell membranes leading to the potential functional and pathogenic consequences detected so far, and their involvement in the development of LBDs.
Author(s): Manzanza NDO, Sedlackova L, Kalaria RN
Publication type: Review
Publication status: Published
Journal: Frontiers in Aging Neuroscience
Year: 2021
Volume: 13
Online publication date: 25/06/2021
Acceptance date: 24/05/2021
ISSN (electronic): 1663-4365
Publisher: Frontiers Media S.A.
URL: https://doi.org/10.3389/fnagi.2021.690293
DOI: 10.3389/fnagi.2021.690293
