α-Synuclein amyloid fibril directly binds to LC3B and suppresses SQSTM1/p62-mediated selective autophagy

Abstract

Dear Editor,

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, which manifests through the abnormal accumulation of pathological amyloid fibrils composed of α-synuclein (α-syn) into Lewy bodies and the deterioration of dopaminergic neurons in the substantia nigra.^1,2,3,4 In addition to α-syn fibrillar aggregation, the disruption of selective autophagy is also tightly linked to the pathogenesis of PD.^5,6 The co-localization of LC3B, the key autophagosome protein in selective autophagy,⁷ and α-syn in the Lewy bodies of PD patients’ brains points towards a potential role of α-syn in modulating selective autophagy.⁸ Yet, the interplay between them has not been mechanistically elucidated.