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Cerebral Lactate Metabolism And Memory: Implications For Alzheimer's Disease, Richard Andrew Harris
Cerebral Lactate Metabolism And Memory: Implications For Alzheimer's Disease, Richard Andrew Harris
Electronic Thesis and Dissertation Repository
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by amyloid plaques that are comprised of aggregated amyloid-beta peptides. These toxic proteins promote mitochondrial dysfunction and neuronal cell death. A shift in metabolism away from oxidative phosphorylation and toward aerobic glycolysis, with the concomitant production of lactate, affords neurons a survival advantage against amyloid-beta toxicity. Recent evidence now suggests that aerobic glycolysis in the brain plays a critical role in supporting synaptic plasticity, learning, and memory. However, the role of aerobic glycolysis and lactate metabolism in AD-mediated cognitive decline is unknown. My objective was to test the hypotheses that aerobic glycolysis …
The Role Of Lactate Dehydrogenase B In Aerobic Glycolysis-Mediated Resistance To Ab Toxicity, Tyler Tam
The Role Of Lactate Dehydrogenase B In Aerobic Glycolysis-Mediated Resistance To Ab Toxicity, Tyler Tam
Electronic Thesis and Dissertation Repository
Alzheimer’s disease is a progressive, neurodegenerative disorder characterized by the accumulation of amyloid β (Aβ) plaques in affected brain regions. Strong evidence indicates that Aβ exerts neurotoxic effects by promoting mitochondrial dysfunction and ROS production, leading to widespread oxidative damage and activation of pro-apoptotic mechanisms. Past investigations suggest that neuronal resistance to Aβ toxicity is partly mediated by a Warburg Effect-like metabolism, in which cells exhibit elevated glycolytic activity and lactate production, while limiting mitochondrial respiration. Elevated lactate dehydrogenase A (LDHA) activity, which catalyzes lactate production from pyruvate, has been demonstrated to counter Aβ-induced oxidative stress and neurotoxicity, however the …