Alpha-synuclein fibril (α-Syn fibril)

Alpha-synuclein fibrils are highly ordered, beta-sheet-rich aggregates formed from misfolded alpha-synuclein protein that accumulate in the brains of patients with synucleinopathies[6]. These fibrils display significant structural polymorphism, with distinct classes and subtle variants revealed by cryo-electron microscopy and solid-state NMR[2][1][4][6]. Mutations in alpha-synuclein’s amino acid sequence affect fibril stability and disease phenotype, with the central non-amyloid-β component (NAC) region being critical for aggregation[1][6]. The fibrils disrupt neuronal function by inducing toxicity, impairing cell signaling, and promoting pathological protein propagation from cell to cell[5][7]. Numerous small molecules, antibodies, and imaging agents have been developed to target these aggregates by preventing formation, destabilizing existing fibrils, or enhancing their clearance, but selective targeting without adverse effects remains a significant therapeutic challenge[2][5][6].

Other names

Alpha-synuclein amyloid fibrilα-Syn amyloid fibrilα-Synuclein aggregateSynuclein fibrilAmyloid fibril of alpha-synuclein

Inhibition of fibril formation; Disruption of preformed fibrils; Clearance of fibrils by immunotherapy (antibodies targeting aggregated forms); Stabilization of monomeric alpha-synuclein; Prevention of cell-to-cell propagation