title: Brain metabolism and Alzheimer's disease: the prospect of a metabolite-based therapy.
abstract: The brain is one of the most energy-demanding organs in the body. It has evolved intricate metabolic networks to fulfill this need and utilizes a variety of substrates to generate ATP, the universal energy currency. Any disruption in the supply of energy results in various abnormalities including Alzheimer's disease (AD), a condition with markedly diminished cognitive ability. Astrocytes are an important participant in maintaining the cerebral ATP budget. However, under oxidative stress induced by numerous factors including aluminum toxicity, the ability of astroctyes to generate ATP is impaired due to dysfunctional mitochondria. This leads to globular, glycolytic, lipogenic and ATP-deficient astrocytes, cerebral characteristics common in AD patients. The reversal of these perturbations by such natural metabolites as pyruvate, α-ketoglutarate, acetoacetate and L-carnitine provides valuable therapeutic cues against AD.
authors.affiliation: Vasu D. Appanna, Faculty of Science and Engineering, Laurentian University, Sudbury, Ontario, P3E 2C6, Canada. Phone: (705) 675-1151, ext. 2112, Fax: (705) 675-4844. E-mail: vappanna@laurentian.ca.
authors.forename: S C
authors.initials: SC
authors.lastname: Thomas
authors.forename: A
authors.initials: A
authors.lastname: Alhasawi
authors.forename: V P
authors.initials: VP
authors.lastname: Appanna
authors.forename: C
authors.initials: C
authors.lastname: Auger
authors.forename: V D
authors.initials: VD
authors.lastname: Appanna
mesh_terms: D000090:Acetoacetates / Q000378:metabolism / Q000627:therapeutic use; D000255:Adenosine Triphosphate / Q000172:deficiency / Q000378:metabolism; D000535:Aluminum / Q000633:toxicity; D000544:Alzheimer Disease / Q000178:diet therapy* / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002331:Carnitine / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007656:Ketoglutaric Acids / Q000378:metabolism / Q000627:therapeutic use; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D019289:Pyruvic Acid / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D000090:Acetoacetates; D007656:Ketoglutaric Acids; C016635:acetoacetic acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D000535:Aluminum; D002331:Carnitine