Fig. 2

Under pathological circumstances, α-synuclein aggregation could potentially take place in affiliation with the cellular membrane or in the cytosol. a Membrane-bound monomeric α-synuclein assumes an α-helical structure, but at elevated levels, the monomer endures conformational change to generate membrane-bound β-sheet structures that self-associate to form oligomers and fibrils. b In the cytoplasm, unfolded monomers fluctuate through conformational space to form unstable dimers, which undergo reorganization to generate oligomers of varying morphologies that eventually transform into fibrils. The erratic accretion of these fibrils leads to the amassing of intracytoplasmic Lewy bodies. c During α-synuclein fibrillogenesis, oligomers and amyloid fibrils are immensely noxious, compromising microtubule dynamics, endoplasmic reticulum–Golgi trafficking, and mitochondrial function. Figures were created with Biorender.com