Objective: The research aimed at preventing the accumulation of Alpha Synuclein in order to prevent it’s accumulation.  It is imperative that we also establish that alpha synuclein, is the faulty protein implicated in the pathogenesis of Parkinson’s Disease (PD). The prevention of the toxic accumulation will be done by stimulating the mobilization of alpha synuclein to the proteosome, where they are degraded, hence, we have a headway towards preventing the accumulation of the toxic protein, invariably slowing down the progression of PD.

Background: The mechanism of the neural death in PD consists of an abnormal accumulation of the the protein.The alpha synuclein binds to ubiquitin to form alpha synuclein-ubiquitin complex, this protein accumulation form proteinous cytoplasmic inclusion called Lewy bodies. Accumulation of this protein alter dopamine metabolism and vesicular packaging, eventually cumulating into formation of metabolites that are toxic to the dopaminergic neurons leading to the death of the cells and decrease in the production of dopamine, which is one of the observable features in patients suffering from PD.

Method: We proposed to knockout Park 4, the gene that codes for parkin, which is the protein, that flags the alpha synuclein for proteasomal targeting, in cell line culture of neurons, When this gene is knocked out, abnormal parkin forms; resulting in the inability of the alpha synuclein to be targeted for degradation.

Results: It is expected that alpha synuclein will accumulate and the accumulation will be monitored by western blotting procedure to see the progression of the oligomerization of alpha synuclein.Arimoclomol will be used to stimulate molecular switches called Rab 1, so that the alpha synuclein is rapidly directed to the proteosome for degradation.

Conclusion: The trafficking action of Rab 1 will enhance alpha synuclein to the right location for hydrolysis.  This will prevent accumulation of the alpha synuclein thereby attenuating the Progression of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/enhancing-the-proteasomal-degradation-of-alpha-synuclein-the-hallmark-to-attenuating-the-progression-of-parkinsons-disease/