Objective: Alpha synuclein aggregation have been indicted in the process of neuronal cell loss in Parkinson’s disease; however, there have been several hypothesis to explain the processes involved in how alpha synuclein aggregates induce cell damage, thus, the research looked into the pathology of Parkinson’s disease based on the localization of alpha synuclein in the mitochondria and how the neuronal injury is caused.

Background: The aim of the research is to link the dysfunctional state of the mitochondria in neurons to the overexpression of alpha synuclein, protein aggregation and synucleinopathies and also, on the flip side, elucidate the role alpha synuclein aggregates play on the alteration of mitochondrial morphology, reduced respiratory chain complex activities and impairment of mitochondrial functions, which further accelerates aggregation of the protein.

Method: Mitochondrial integrity, respiration and health were examined using several markers of mitochondrial dynamics and stress response and by measuring the rate of oxygen consumption in neuronal cells, expressing oligomeric alpha synuclein.

Results: Alpha synuclein aggregation in presynaptic neurons are said to alter dopamine metabolism and recyclying in the cytoplasm of the neuron, the impaired metabolism has been linked to release of oxidative radicals which find their way to the mitochondria, initiating oxidative stress and damage. Additionally, oligomeric forms of alpha synuclein have been found in the mitochondria which induces a decrease in Sirtuin3, SIRT3, via reduced phosphorylation of cAMP-response Element Binding protein, (CREB), decrease in the phosphorylation of Adenosine Monophosphate activated Protein Kinase, (AMPK) and biogenesis. Increase phosphorylation of dynamin-related protein, (DRP1), which is indicative of impaired mitochondria dynamics and also reduced oxygen consumption, suggesting deficit in mitochondria respiration.

Conclusion: The findings suggest that therapeutic intervention targeted at increasing Mitochondrial SIRT3 might be imperative to attenuate mitochondrial dysfunction induced by alpha synuclein aggregation, towards normalising mitochondrial respiratory chain function, homeostasis, metabolism. Bioenergetics and mitochondrial protection.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-induction-of-mitochondrial-damage-by-alpha-synuclein-in-parkinsons-disease/