The important role of alpha synuclein in mediating central and peripheral immune responses

The normal function of alpha synuclein (aSyn) is poorly understood, but it is implicated in the regulation of vesicle dynamics, and is important in neuronal plasticity. aSyn is the major component of Lewy bodies, the pathologic hallmark of Parkinson's disease (PD). In addition, extracellular aSyn has been proposed to have a role in neuroinflammation in PD. Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by the formation of focal demyelinating plaques in the brain and spinal cord. It has been demonstrated that aSyn is upregulated in neurons and glia in spinal cord (SC) lesions of an experimental autoimmune encephalomyelitis (EAE) induced mice. In addition, MS patients showed increased levels of aSyn in the cerebrospinal fluid (CSF) as compared with healthy controls. We aim to evaluate the role of aSyn in mediating neuroinflammation. We discovered that gene allocated to PD impairs degradation of aSyn in microglia cells and enhances secretion of pro-inflammatory cytokines. We postulated that aSyn knockout mice would display a reduction in neuroinflammation in an EAE model. Surprisingly, we discovered that the absence of aSyn exacerbates EAE disease progression. Both aSyn knockout CD4+ T cells and antigen presenting cells showed an increase in secretion of pro-inflammatory cytokines as compared to WT mice. Furthermore, we discovered a reduction in expression levels of aSyn in immunized splenocytes suggesting that aSyn is a negative regulator of the activation process. Continued research on the expression of aSyn in immune cells may increase our understanding of its physiological function and its role in mediating neuroinflammation in neurological diseases, such as MS and PD, towards future therapeutic application.