| Popis: |
α-Synuclein predominantly expressed in the brain is a small acidic protein containing three domains namely N-terminal lipid-binding α-helix, amyloid-binding central domain (NAC), and C-terminal acidic tail. The physiological functions of this protein remain poorly understood. α-Synuclein localizes specifically to the nerve terminal and has been extensively described to take active task in the regulation of release of neurotransmitter at the presynapse in brain. Accumulating evidence suggests that prefibrillar species, and aggregated form of α-synuclein, are accountable for the pathogenicity of Parkinson’s disease (PD). Larger oligomers of α-synuclein exhibited to impair many functions of neuronal cells including: impairment of synaptic functions, impairment of the mitochondrial and the endoplasmic reticulum functions, and the impairment of protein degradation pathways. Oligomers/protofibrils once accumulated inside or outside cells may cause a lethal effect on the synapse, which may cause disruption of the neurotransmission. The oligomeric α-synuclein species has also the property of spreading between neuronal cells, either as drifting proteins or via extracellular vesicles, and thus spreading the toxic effects in different parts of the brain. Although several mutations in α-synuclein gene have been known that causes familial PD in human, the mechanisms that elevate the accumulation and aggregation of α-synuclein protein are not well addressed. Considering of the mechanism of aggregation of α-synuclein protein and targeting the toxic functions of this protein in brain cells including dysregulated mitochondrial functions may lead to novel therapeutic approaches in Parkinson’s disease. |
