Synuclein Proteoforms: Role in Health and Disease

Area of Science:

• Neurobiology
• Molecular Medicine
• Protein Biochemistry

Background:

• Synucleins (α, β, γ) are intrinsically disordered proteins vital for neuronal function.
• Pathological aggregation of synucleins underlies synucleinopathies such as Parkinson's disease.
• The full biological significance of diverse synuclein proteoforms remains incompletely understood.

Purpose of the Study:

• To systematically review the structural and functional diversity of synuclein proteoforms.
• To explore the roles of β- and γ-synucleins in modulating α-synuclein aggregation.
• To integrate knowledge on synuclein proteoforms, their interactions, aggregation, and implications in neurodegeneration and beyond.

Main Methods:

• Systematic literature review and knowledge synthesis.
• Analysis of recent advancements in molecular imaging and proteomic techniques.
• Investigation of regulatory effects and aggregation pathways of synuclein proteoforms.

Main Results:

• Synuclein proteoforms exhibit significant structural and functional heterogeneity.
• β- and γ-synucleins influence α-synuclein aggregation, with distinct physiological roles.
• Synucleins are implicated in both central nervous system and peripheral tissue functions, including immune regulation.

Conclusions:

• Understanding synuclein proteoform complexity is crucial for developing targeted therapies for synucleinopathies.
• Advances in characterization techniques facilitate the study of synuclein proteoforms.
• Bridging translational research and molecular neurobiology is essential for addressing synuclein-related disorders.