Accumulation of Alpha-Synuclein Aggregates and it's Causes, Eventually Lead to Neurodegeneration Resulting into Pathogenesis of Parkinson's Disease

Parkinson's disease (PD) is the second most common neurodegenerative (ND) disorder known to occur all over the world, mostly in the old-aged people. PD is recognised as an α-Synucleinopathy which features the accumulation of ND protein that is alpha-synuclein (α-syn), in neuronal and glial cells. It is acquainted with poor neuronal signalling and impaired neurons mainly in the substantia nigra part of the central nervous system. Aggregates of α-synuclein were discovered to be the building blocks of Lewy Bodies(LB), which is the pathological hallmark of PD. Lewy pathology accumulation resulted in progressive loss of dopaminergic neurons in the substantia nigra pars compacta. On the other hand, astrocytes are major and most abundant glial cell type in the brain, which are found to degrade α-syn to some extent. They can transfer the protein from one neuron to other directly or through Tunneling nanotubes (TNTs). However, due to over accumulation, over longer period of time it results into mitochondrial abnormalities and detrimental cellular processes in astrocytes therefore leading to glial cell death. The abnormal ND protein accumulation is identified to be caused due to a range of external and internal factors which dysrupts the intracellular and extracellular activities of neuronal cells. Specifically, α-syn aggregates might have been triggered by various factors such as: aging, environmental-oxidative stress or inflammation, genetic mutations and polymorphisms, impaired cellular processes like protein clearance systems (UPS and ALP) and dysfunction of mitochondrial and lysosomal pathways. α-Syn portrays a vicious cycle wherein damage to proteasomal and lysosomal systems could cause α-Syn to accumulate, and thereby increased levels of α-Syn could inhibit the proteasome and lysosomal systems, ultimately leading to the formation of oligomers and aggregates, which results into neurodegeneration and clinical dysfunction. It causes mitochondrial and lysosomal dysfunction which eventually leads to cell death and neurodegeneration leading to PD pathogenesis. Citation: Janhavi Dhore. "Accumulation of Alpha-Synuclein Aggregates and it's Causes, Eventually Lead to Neurodegeneration Resulting into Pathogenesis of Parkinson's Disease." Global Research and Development Journal For Engineering 6.6 (2021): 12 - 18.