Alpha-Synuclein in Neurodegeneration: From Shared Biology to Disease-Specific Phenotypes - PubMed

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Alpha-synuclein (αSyn) is a key protein in the nervous system linked to synucleinopathies like Parkinson's disease (PD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).
The review highlights that αSyn-driven diseases emerge from interactions between cell-type-specific roles, subcellular environments, post-translational modifications (PTMs), and co-pathology.
αSyn has physiological roles in neurons and glia (astrocytes, oligodendrocytes, microglia) and functions differently in synaptic and nuclear compartments.
Pathological diversity in synucleinopathies is shaped by molecular transitions (e.g., pS129 modification) that convert functional αSyn assemblies into pathogenic conformers.
The study suggests that understanding these multidimensional aspects of αSyn biology can lead to next-generation biomarkers and precision therapies for distinct disorders.

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