Neurotoxic or neuroprotective: Post-translational modifications of α-synuclein at the cross-roads of functions

Parkinson's disease is the second most prevalent neurodegenerative disease. The loss of dopaminergic neurons in the substantia nigra is one of the pathological hallmarks of PD. PD also belongs to the class of neurodegenerative disease known as 'Synucleinopathies' as alpha-synuclein is responsible for disease development. The presence of aggregated alpha-synuclein associated with other proteins found in the Lewy bodies and Lewy neurites in the substantia nigra and other regions of the brain including locus ceruleus, dorsal vagal nucleus, nucleus basalis of Meynert and cerebral cortex is one of the central events for PD development. The complete biological function of alpha-synuclein is still debated. Besides its ability to propagate, it undergoes various post-translational modifications which play a paramount role in PD development and progression. Also, the aggregation of alpha-synuclein is modulated by various post-translational modifications. Here, we present a summary of multiple PTMs involved in the modulation of alpha-synuclein directly or indirectly and to identify their neuroprotective or neurotoxic roles, which might act as potential therapeutic targets for Parkinson's disease. (C) 2021 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.