title: Amino Acid Catabolism in Alzheimer's Disease Brain: Friend or Foe?
abstract: There is a dire need to discover new targets for Alzheimer's disease (AD) drug development. Decreased neuronal glucose metabolism that occurs in AD brain could play a central role in disease progression. Little is known about the compensatory neuronal changes that occur to attempt to maintain energy homeostasis. In this review using the PubMed literature database, we summarize evidence that amino acid oxidation can temporarily compensate for the decreased glucose metabolism, but eventually altered amino acid and amino acid catabolite levels likely lead to toxicities contributing to AD progression. Because amino acids are involved in so many cellular metabolic and signaling pathways, the effects of altered amino acid metabolism in AD brain are far-reaching. Possible pathological results from changes in the levels of several important amino acids are discussed. Urea cycle function may be induced in endothelial cells of AD patient brains, possibly to remove excess ammonia produced from increased amino acid catabolism. Studying AD from a metabolic perspective provides new insights into AD pathogenesis and may lead to the discovery of dietary metabolite supplements that can partially compensate for alterations of enzymatic function to delay AD or alleviate some of the suffering caused by the disease.
authors.affiliation: Department of Biomedical Sciences, East Tennessee State University College of Medicine, Johnson City, TN 37614, USA.
authors.forename: Jeddidiah W D
authors.identifier: 0000-0002-5529-4945
authors.initials: JW
authors.lastname: Griffin
authors.affiliation: Department of Biomedical Sciences, East Tennessee State University College of Medicine, Johnson City, TN 37614, USA.
authors.forename: Patrick C
authors.identifier: 0000-0002-4591-6798
authors.initials: PC
authors.lastname: Bradshaw
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008660:Metabolism; D009474:Neurons / Q000378:metabolism*
chemical_list: D000596:Amino Acids