Abstract
Several intrinsically disordered proteins have been implicated in the process of amyloid fibril formation in neurodegenerative disease, and developing approaches to inhibit the aggregation of these intrinsically disordered proteins is critical for establishing effective therapies against disease progression. The aggregation pathway of the intrinsically disordered protein alpha-synuclein, which is implicated in several neurodegenerative diseases known as synucleinopathies, has been extensively characterized. Less attention has been leveraged on beta-synuclein, a homologous intrinsically disordered protein that co-localizes with alpha-synuclein and is known to delay alpha-synuclein fibril formation. In this review, we focus on beta-synuclein and the molecular-level interactions between alpha-synuclein and beta-synuclein that underlie the delay of fibril formation. We highlight studies that begin to define alpha-synuclein and beta-synuclein interactions at the monomer, oligomer, and surface levels, and suggest that beta-synuclein plays a role in regulation of inhibition at many different stages of alpha-synuclein aggregation.