Bodha, Bhaarti (2019) Cholesterol metabolism in spinocerebellar ataxias: trying to unravel the underlying mechanism in the neurodegenerative disorders. Master's Thesis / Essay, Biomedical Sciences.
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Abstract
Abstract Autosomal Dominant Spinocerebellar Ataxia’s (ADCAs) are a subset of hereditary spinocerebellar ataxias showing atrophy of the cerebellum and loss or Purkinje cells (PCs) leading to uncoordinated movement and gait. Most SCA subtypes can be attributed to CAG trinucleotide repeat expansions with several lengths, leading to protein misfolding and aggregation mainly in the cerebellum. Defects in cholesterol metabolism have been observed in SCA and it has already been shown in other neurological diseases such as Alzheimer’s disease, Huntington disease and Niemann-Pick type C that it contributes to neurodegeneration. A defective clearance of cholesterol might be the cause of cholesterol accumulation observed in SCA. CYP46A1 is responsible for the turnover of cholesterol to 24-OHC and be excreted from the brain. In SCA, CYP46A1 levels are decreased, leading to cholesterol accumulation in the brain. In addition, CYP46A1 mediates autophagy in the brain. When CYP46A1 levels are decreased, autophagy is attenuated due to defects in late-endosomes and leads to aggregation of the misfolded proteins seen in SCA. The aggregated proteins cause Endoplasmatic reticulum (ER) stress. ER stress might be the start of a vicious cycle of cholesterol synthesis and defective clearance, leading to cholesterol accumulation and contributes to pathology.
| Item Type: | Thesis (Master's Thesis / Essay) |
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| Supervisor name: | Verbeek, D.S. |
| Degree programme: | Biomedical Sciences |
| Thesis type: | Master's Thesis / Essay |
| Language: | English |
| Date Deposited: | 24 Dec 2019 09:52 |
| Last Modified: | 24 Dec 2019 09:52 |
| URI: | https://fse.studenttheses.ub.rug.nl/id/eprint/21357 |
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