Parkinson’s disease (PD) is the second most common neurodegenerative disorder primarily affecting the aging population over the age of sixty. Characterized by the significant degeneration of dopaminergic (DAergic) neurons of the substantia nigra causing severe motor dysfunction. Although the exact pathogenesis of this disease is still unknown endoplasmic reticulum stress and mitochondrial dysfunction are believed to play a role. PD is diagnosed after severe DAergic neuron degeneration, and yet is still often misdiagnosed. There is a need for a definitive diagnostic test for the early detection of PD. Current therapies only relieve symptoms and do not stop disease progression. Neurotrophic factors (NTF) are naturally occurring proteins that promote the survival, differentiation and maintenance of neurons and present a promising candidate for the treatment of PD. Cerebral dopamine neurotrophic factor (CDNF) is a novel NTF that protects and rescues DAergic neurons. The present study investigated the role of DAergic activity and CDNF mRNA expression in C. elegans, as well as understanding how does PD affect the endogenous levels of CDNF protein and mRNA expression.
We demonstrated that of the various dopamine (DA) synthesis and transport mutants tested, the impaired synthesis of DA from levodopa is linked to the up regulation of CDNF. Also, following unilateral 6-hydroxydopamine (6-OHDA) lesioning protein and mRNA expression of CDNF was not affected implicating ER stress as inducing a possible compensatory up regulation of CDNF, thus returning levels to normal. CDNF mRNA expression was determined to decline with age and possibly increase ones vulnerability to developing a neurodegenerative disorder. An increase mRNA expression of CDNF in the PD patient population was found to be specific to platelets. Stroke patients showed an increase in CDNF expression in whole blood. In conclusion, these findings highlight the importance of the relationship between CDNF and ER stress and warrants further investigation. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/16238 |
| Date | 11 1900 |
| Creators | Siddiqi, Asim |
| Contributors | Mishra, Ram, Neuroscience |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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