Navigating through the complexities of synucleinopathies: Insights into pathogenesis, heterogeneity, and future perspectives.

Abstract

The aggregation of alpha-synuclein (aSyn) represents a neuropathological hallmark observed in a group of neurodegenerative disorders collectively known as synucleinopathies. Despite their shared characteristics, these disorders manifest diverse clinical and pathological phenotypes. The mechanism underlying this heterogeneity is thought to be due to the diversity in the aSyn strains present across the diseases. In this perspective, we will explore recent findings on aSyn strains and discuss recent discoveries about Lewy bodies' composition. We further discuss the current hypothesis for aSyn spreading and emphasize the emerging biomarker field demonstrating promising results. A comprehension of these mechanisms holds substantial promise for future clinical applications. This understanding can pave the way for the development of personalized medicine strategies, specifically targeting the unique underlying causes of each synucleinopathy. Such advancements can revolutionize therapeutic approaches and significantly contribute to more effective interventions in the intricate landscape of neurodegenerative disorders.