Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Pharmacology and Toxicology

Supervisor

Dr. Michael F. Jackson and Dr. John F. MacDonald

Abstract

Many neurodegenerative diseases, including Alzheimer’s Disease, are associated with ER stress. It is suggested that plasma membrane channels contribute to the increased ionic influx and subsequent cell death in response to ER stress. Pannexin channels, which have been implicated in various pathophysiological conditions, are a suitable candidate for facilitating this response. However, mechanisms of pannexin channel activation are poorly defined. I investigated the potential regulation of pannexin activity by the ER stress sensor, STIM. It was hypothesized that pannexin channel activation during ER stress is contingent on the recruitment of STIM proteins. In neurons, pannexin activation was observed in response to pharmacological ER stressors as well as Aβ42. Moreover, I identified STIM as a key signaling component promoting pannexin activation under ER stress in HEK cells, though not in neurons. In conclusion, pannexin activation is coupled to ER stress in neurons; however, the underlying molecular mechanism remains unknown.


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