The amplification of α-synuclein amyloid fibrils.

Amyloid fibrils formed by α-synuclein are a hallmark of a range of neurodegenerative diseases, notably Parkinson's disease, multiple system atrophy (MSA), and dementia with Lewy bodies, collectively known as synucleinopathies. Recent years have seen an increasing understanding of the structural architecture and diversity of α-synuclein amyloid fibrils. Furthermore, our mechanistic understanding of the formation of these structures has also experienced significant progress. Here, I provide a concise overview of the current state of knowledge of how α-synuclein amyloid fibrils can be amplified, i.e., increase in number. The main emphasis is thereby on the process of secondary nucleation, i.e., the generation of new amyloid fibrils catalyzed by existing fibrils. A detailed understanding of fibril amplification is relevant in the context of the spread of pathology in the central nervous system of synucleinopathy patients. In addition, it can also be exploited in the framework of diagnostic approaches collectively known as seed amplification assays (SAAs). In such assays, the minute quantities of α-synuclein fibrils present in biological fluids are amplified and possibly quantified for disease diagnostics.