BME PhD Preliminary Exam announcement for Anna Alford (Riyi Shi, advisor)

Everyone is invited to attend the public presentation beginning at 12:00pm.

Title: The Pathological Role of Acrolein Scavenging and ALDH2*2 in EAE Mice

Date: July 22,^, 2024

Time: 12:00pm

Location: DLR 131

Committee:

Dr. Riyi Shi (Major)

Adam Kimbrough 

Elsje Pienaar

Jessica Fortin

Abstract:

                Multiple Sclerosis (MS) is a severely debilitating, demyelinating disease with no known cure. Acrolein, a reactive aldehyde, has recently been implicated in the pathology of neurodegenerative diseases, including MS, for its ability to directly degrade myelin. Therefore, major efforts have been expended to determine if acrolein could serve as a viable therapeutic target in MS, as current treatments only provide symptomatic relief without significantly altering the disease pathology. Our lab has demonstrated that several acrolein scavengers, such as hydralazine, dimercaprol, and phenelzine, are effective in alleviating MS symptoms in an animal model, experimental autoimmune encephalomyelitis (EAE) mice. In addition to exogenous applications, we tested the administration of Alda-1, a drug that activates an endogenous acrolein-scavenging enzyme, ALDH2. Alda-1 application also demonstrates a significant alleviation of EAE symptoms. To further understand the role of acrolein in EAE, we look at a clinically relevant genotype in mice, ALDH2*2, a human enzymatic deficiency suffered by millions. In this genotype, ALDH2 efficiency is dramatically reduced compared to healthy individuals. Thus, we hypothesize that ALDH2*2 EAE mice will suffer dramatically worse symptoms than wild-type EAE controls. As suspected, we have observed significant deficits in motor and behavioral symptoms in addition to an increase in several pathological hallmarks of MS, including inflammation and demyelination, in ALDH2*2 EAE mice compared to their wild-type counterparts. Taken together, our data provides additional support that acrolein plays a critical role in MS pathology and suggests that ALDH2 potentiation could serve as an effective treatment, particularly in individuals with ALDH2*2 deficiency.