β-Synuclein: An Enigmatic Protein with Diverse Functionality

alpha-Synuclein (alpha S) is a small, unstructured, presynaptic protein expressed in the brain. Its aggregated form is a major component of Lewy bodies, the large proteinaceous deposits in Parkinson's disease. The closely related protein, beta-Synuclein (beta S), is co-expressed with alpha S. In vitro, beta S acts as a molecular chaperone to inhibit alpha S aggregation. As a result of this assignation, beta S has been largely understudied in comparison to alpha S. However, recent reports suggest that beta S promotes neurotoxicity, implying that beta S is involved in other cellular pathways with functions independent of alpha S. Here, we review the current literature pertaining to human beta S in order to understand better the role of beta S in homeostasis and pathology. Firstly, the structure of beta S is discussed. Secondly, the ability of beta S to (i) act as a molecular chaperone; (ii) regulate synaptic function, lipid binding, and the nigrostriatal dopaminergic system; (iii) mediate apoptosis; (iv) participate in protein degradation pathways; (v) modulate intracellular metal levels; and (vi) promote cellular toxicity and protein aggregation is explored. Thirdly, the P123H and V70M mutations of beta S, which are associated with dementia with Lewy bodies, are discussed. Finally, the importance of post-translational modifications on the structure and function of beta S is reviewed. Overall, it is concluded that beta S has both synergistic and antagonistic interactions with alpha S, but it may also possess important cellular functions independent of alpha S.

Automated summary

This article reviews the current literature on human βS to better understand its role in homeostasis and pathology. The structure of βS is discussed, as well as its ability to act as a molecular chaperone, regulate synaptic function and other cellular pathways. The mutations associated with dementia with Lewy bodies are also explored, along with the impact of post-translational modifications on βS.