Essay: Aberrant synuclein expression and its role in pathogenesis in dopaminergic neurons

Berbers, B.S.W. (2014) Essay: Aberrant synuclein expression and its role in pathogenesis in dopaminergic neurons. Bachelor's Thesis, Biology.

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Abstract

The most occurring age-related movement disorder is Parkinson’s disease, which has proteineous inclusions called Lewy bodies as its main cytopathological hallmark. These inclusions consist mostly of α-synuclein. This knowledge combined with genetic evidence implicates α-synuclein in Parkinson’s disease. Non-pathologically, α-synuclein is a chaperone protein to help SNARE-complex formation during vesicle exocytosis in the synapse. However, aberrant synuclein can set multiple pathological pathways in motion leading to cytotoxicity and neurodegeneration. Aggregation of α-synuclein proteins results in soluble oligomers. This form of oligomeric, not fully fibrillar, α-synuclein is thought to exert detrimental effects on cytoplasmic and intra cellular membranes by forming pore-like structures, which can change calcium and dopamine homeostasis. Changes in homeostasis can increase oxidative stress and cause both lysosomal and ubiquitin dysfunction, additionally increasing intracellular α-synuclein concentration. Finally, malfunctioning of the dopamine release can cause spines of connecting neurons to decrease, leading to further neurodegeneration. Therefore, feed-forward amplification loops are now commonly thought to induce apoptosis in neurons, each aberrant α-synuclein pathway enhancing the toxicity of others.

Item Type:	Thesis (Bachelor's Thesis)
Degree programme:	Biology
Thesis type:	Bachelor's Thesis
Language:	English
Date Deposited:	15 Feb 2018 07:56
Last Modified:	15 Feb 2018 07:56
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/11642

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