Dissertation/Thesis Abstract

Aging, Stress, and Pathogenesis of Parkinson's Disease: Studies Using C. elegans
by Cooper, Jason Fisk, Ph.D., Van Andel Research Institute, 2018, 208; 10747486
Abstract (Summary)

Parkinson’s disease (PD) is an adult onset neurodegenerative disease that is characterized by deficiencies in movement, cognition, and Lewy body neuropathology within the brain. Motor and cognitive deficiencies progressively worsen through the course of disease concurrent with increasing neuropathology and neurodegeneration. Approximately 10–15% of PD patients have a family history of PD with a confirmed genetic cause. Presently PD pathogenesis is incompletely understood and there are no treatments capable of halting or reversing this disease. The extended disease-course and age-dependent nature of PD, especially in genetic cases where a mutation is present from birth, affirm that aging itself is the most important risk factor for disease. We hypothesize that specific cellular changes that occur during the normal process of aging confer susceptibility to disease-causing mutations which, while tolerated at younger ages, contribute to disease with age. Accurate animal models of PD and aging provide the ability to elucidate disease mechanisms and explore novel strategies targeting the aging process. To test the role of aging in PD we utilize the nematode Caenorhabditis elegans because this animal has been used extensively to study animal aging at a cellular level. We confirm that disease phenotypes in genetic C. elegans models of PD such as neurodegeneration, protein aggregation, and mitochondrial deficits are proportional to this organism’s brief lifespan. This indicates that PD progresses according to biological age and not merely to chronological time. As a proof-of-principle we also show that delaying aging by mutation of the gene encoding the insulin-IGF receptor, daf-2, can rescue multiple deficits present in nematode models of PD. Overall we demonstrate that biological aging is a crucial for the development of various PD associated phenotypes and that delaying aging is sufficient to delay these phenotypes. Therefore targeting aging itself may be a sound strategy for the halting or the prevention of PD.

Indexing (document details)
Advisor: Raamsdonk, Jeremy Van
Commitee: Brundin, Patrik, Collier, Timothy, Ma, Jiyan
School: Van Andel Research Institute
Department: Biomedical
School Location: United States -- Michigan
Source: DAI-B 79/08(E), Dissertation Abstracts International
Subjects: Biology, Molecular biology, Neurosciences
Keywords: Aging, C. elegans, Parkinson's desease, Pathogenesis, Stress
Publication Number: 10747486
ISBN: 9780355768626
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