Lanci, Luigina (2022). Neuronal differentiation and neurodegeneration: the role of Nogo-A? (Unpublished). (Dissertation, Vetsuisse)
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Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. One of the main characteristics of this disorder is the degenerative loss of midbrain dopaminergic (DAergic) neurons of the substantia nigra pars compacta (SNpc). Antagonization of the neurite outgrowth inhibitor Nogo-A, encoded by the RTN4 gene, was demonstrated to improve axonal repair after spinal cord injuries. While the role of Nogo-A in the pathogenesis of PD is largely unknown, interest on its effects in PD is growing, as Nogo-A expression levels were found to be high in DAergic neurons of rat ventral mesencephalon in the SNpc.
In this study, a stable RTN4-KO SH-SY5Y cell line has been established, and the role of Nogo-A-KO under neuronal differentiation and its impact on related pathways has been investigated. The expression of DAergic markers (TH, Nurr1, α-syn) was increased in RTN4-KO cells, indicating an influence of Nogo-A on the DAergic phenotype. No difference in protein levels of the synaptic plasticity marker synaptophysin and the mitochondrial markers Mfn2 and OPA1 was found when compared to control cells. Markers for neuronal differentiation (GSK3β, β-catenin, MAP-2) were not altered in RTN4-KO cells, while protein levels of other markers related to differentiation and neurodegeneration (Akt, MAPK) changed. The role of Nogo-A in these pathways needs to be investigated further in an experimental model of PD.
Item Type: |
Thesis (Dissertation) |
|---|---|
Division/Institute: |
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Veterinary Pharmacology and Toxicology |
UniBE Contributor: |
Lanci, Luigina |
Subjects: |
500 Science > 570 Life sciences; biology |
Language: |
English |
Submitter: |
Angélique Ducray |
Date Deposited: |
02 Feb 2023 09:09 |
Last Modified: |
02 Feb 2023 23:27 |
Uncontrolled Keywords: |
Parkinson’s disease, CRISPR/Cas9, Nogo-A, neuronal differentiation, SH-SY5Y cells |
BORIS DOI: |
10.48350/178199 |
URI: |
https://boris.unibe.ch/id/eprint/178199 |
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