Alpha-Synuclein Aggregation and Spread: Implications for the Pathology and Progression of Neurodegenerative Diseases

• DOI: 10.20944/preprints202312.0569.v1
• Publication Date: 2023-12-11T00:37:23Z
• Authors: Alin Bose Johnson; Niharika Modi; Krithik N. Kamath; Raman Rajeshkumar; Vasanth Raj Palan...
• Keywords: Synucleinopathies; Lewy body; Synuclein; Amyloid (mycology)

Neurodegenerative diseases, including Alzheimer's, Huntington's, Parkinson’s, and Amyotrophic Lateral Sclerosis, involve neuron degeneration linked to the misfolding of amyloidogenic proteins, resulting in β-sheet-enriched aggregates. This phenomenon disrupts normal folding proteins critical for cellular function. Genetic mutations, proteolytic cleavage, oxidative stress, aging contribute misfolding. Parkinson's disease (PD) is closely tied alpha-synuclein (αS) misfolding, with A53T mutation Lewy bodies (LB) PD brains pivotal understanding mechanism. Other synuclein homologues (βS, γS) further synucleinopathies. Mutants (A30P, A53T, E46K, H50Q, G51D) underscore αS's role development. concise review focuses on molecular pathological aspects neurodegenerative emphasizing αS PD. The integration genetic, structural, mechanistic insights highlights disorders. complexity, paving way future therapeutic strategies targeting protein aggregation.