Investigation of the role of Mitochondrial Dysfunction as a trigger for neurodegeneration in Alzheimer’s Disease

Alzheimer’s disease (hereafter AD) is a progressive neurodegenerative disorder that affects cognitive function and memory of the patient. It results from plaques formed by the abnormal cleavage of the Amyloid Precursor Protein (APP), which result in the formation of 42 amino acid polypeptide, also known as amyloid beta 42 (Aβ42). Accumulation of Aβ42 peptide triggers cell death in the neuronal cell population of central nervous system. However, the trigger for this abnormal cell death is unknown. A possible explanation involves the role of mitochondrial dysfunction as the trigger for neurodegeneration. Mitochondria are involved in vital cellular functions, including ATP production, calcium ion homeostasis, reactive oxygen species production, and apoptosis. My hypothesis is that mutations in genes regulating mitochondrial health may play a role in neurodegeneration observed in AD mediated neurodegeneration. The rationale behind this hypothesis is, mitochondria are present in all neurons and mitochondrial function impairment results in cell suicide. It is known that trigger for cell death initiates from the mitochondria. Therefore, mitochondria might play an important role in Aβ42 mediated neuronal death. In order to investigate these issues, a Drosophila melanogaster eye model is used with the Gal4/UAS to misexpress the human Aβ42 polypeptide in the photoreceptor neurons of the fly retina. I propose to test the role of mitochondria in AD using candidate gene approach. These studies swill have significant bearings on understanding the etiology of AD and identification of biomarkers for early detection of this disease.https://ecommons.udayton.edu/stander_posters/1881/thumbnail.jp