Alpha-synuclein was discovered 30 years ago. This small protein is implicated in several neurodegenerative diseases including Alzheimer's and Parkinson's. Extensive literature has flourished, describing its physiological and pathological roles in various models and contexts. Among others, alpha-synuclein regulates processes such as vesicular trafficking, but it is mainly recognized as a pathological hallmark of Parkinson's disease as it forms aggregates within brain cells. These aggregates can spread from cell to cell, and drive disease progression through a variety of mechanisms. Accordingly, alpha-synuclein has a very strong potential as a therapeutic target.

A tremendous step forward in the early diagnosis of Parkinson's disease was recently achieved, with the large-scale validation of a seed amplification assay that uses alpha-synuclein as a biomarker. This will greatly advance our ability to design and evaluate the success of clinical trials. However, our accumulated knowledge of alpha-synuclein biology has not yet translated into its use as a therapeutic target. In this Research Topic, we are aiming at contributing to fill this gap by providing an overview of the consensuses that the field has reached regarding the Physiopathological functions of alpha-synuclein and its involvement in disease onset and progression at the cellular and molecular level, beyond its importance as a biomarker. This Research Topic will highlight innovative directions and ground-breaking recent/new findings to bridge the gap between knowledge and therapy.

This Research Topic is purposedly targeted to cover very diverse areas of interest in the field and reach a broad audience. Authors are encouraged to highlight connections between several areas of interest to create an integrated view of alpha-synuclein biology. The specific themes and sub-themes include:

• Alpha-synuclein in neurodegenerative diseases including Parkinson's (loss- vs gain-of-function; toxicity; diagnostic/therapeutic potential; modifiers of alpha-synuclein pathology; integration of alpha-synuclein in Parkinson's-relevant pathways)
• Alpha-synuclein aggregation
• Intercellular spread of alpha-synuclein aggregates
• Physiology of alpha-synuclein (functions in vesicular trafficking and other processes, importance of post-translational modifications)
• Models and tools to study alpha-synuclein (animal models (invertebrate, vertebrate), human models, molecular tools).

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Frontiers in Molecular Neuroscience

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