ß-Synuclein: An Enigmatic Protein with Diverse Functionality.

ABSTRACT

α-Synuclein (αS) 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, ß-Synuclein (ßS), is co-expressed with αS. In vitro, ßS acts as a molecular chaperone to inhibit αS aggregation. As a result of this assignation, ßS has been largely understudied in comparison to αS. However, recent reports suggest that ßS promotes neurotoxicity, implying that ßS is involved in other cellular pathways with functions independent of αS. Here, we review the current literature pertaining to human ßS in order to understand better the role of ßS in homeostasis and pathology. Firstly, the structure of ßS is discussed. Secondly, the ability of ßS 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 ßS, which are associated with dementia with Lewy bodies, are discussed. Finally, the importance of post-translational modifications on the structure and function of ßS is reviewed. Overall, it is concluded that ßS has both synergistic and antagonistic interactions with αS, but it may also possess important cellular functions independent of αS.