Alpha-synuclein induced apoptosis and proliferation interacted with CD44 in human lymphocytes

Abstract

Human ?-synuclein is a 140 amino acid protein with little or no secondary structure. The ?-synuclein is expressed at high levels in the brain and enriched in neural synaptic terminals but its physiological function remains largely unknown. More recently, ?-synuclein has been shown to be one of the principal componets of Lewy bodies, neuronal inclusions that are found in diverse human neurodegenrerative disorder including the Lewy body variant of Alzeheimer’s disease, diffuse Lewy body disease, Parkinson’s disease, multiple system atrophy. Therefore, ? -synuclein and its abnormal protein aggregation have been thought to play a role in the pathogenesis of these neurodegenerative diseases known as ?-synucleinopathies. In order to understand their etiology and pathogenesis, it is crucial to identify the normal function of ?-synuclein. It was previously reported that the splicing variant of ? -synuclein is expressed in heart, skeletal muscle, and pancreas. In our study, we identified the expression in spleen and confirmed the expression of ?-synuclein in isolated human PBMC. The physiological role in lymphocytes showed induction of apoptosis with Caspase-8 and Caspase-9 activation. And also they showed enhanced expression of CD44, a multifunctional cell surface glycoprotein, on human lymphocytes. We further found that the stimulation of CD44 triggered intracellular ?-synuclein expression, reversly. There was involvement of multiple signaling pathways, the activation of PKC, Ras oncoprotein. These Results suggest that ?-synuclein is participates in cell adhension and viability in lymphocytes.