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Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer's disease.
Mitochondrion. 2007 Sep; 7(5):297-310.M

Abstract

Several studies have demonstrated aberrations in the Electron Transport Complexes (ETC) and Krebs (TCA) cycle in Alzheimer's disease (AD) brain. Optimal activity of these key metabolic pathways depends on several redox active centers and metabolites including heme, coenzyme Q, iron-sulfur, vitamins, minerals, and micronutrients. Disturbed heme metabolism leads to increased aberrations in the ETC (loss of complex IV), dimerization of APP, free radical production, markers of oxidative damage, and ultimately cell death all of which represent key cytopathologies in AD. The mechanism of mitochondrial dysfunction in AD is controversial. The observations that Abeta is found both in the cells and in the mitochondria and that Abeta binds with heme may provide clues to this mechanism. Mitochondrial Abeta may interfere with key metabolites or metabolic pathways in a manner that overwhelms the mitochondrial mechanisms of repair. Identifying the molecular mechanism for how Abeta interferes with mitochondria and that explains the established key cytopathologies in AD may also suggest molecular targets for therapeutic interventions. Below we review recent studies describing the possible role of Abeta in altered energy production through heme metabolism. We further discuss how protecting mitochondria could confer resistance to oxidative and environmental insults. Therapies targeted at protecting mitochondria may improve the clinical outcome of AD patients.

Authors+Show Affiliations

Nutrition and Metabolism Center, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609-1673, USA. hatamna@chori.orgNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

17625988

Citation

Atamna, Hani, and William H. Frey. "Mechanisms of Mitochondrial Dysfunction and Energy Deficiency in Alzheimer's Disease." Mitochondrion, vol. 7, no. 5, 2007, pp. 297-310.
Atamna H, Frey WH. Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer's disease. Mitochondrion. 2007;7(5):297-310.
Atamna, H., & Frey, W. H. (2007). Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer's disease. Mitochondrion, 7(5), 297-310.
Atamna H, Frey WH. Mechanisms of Mitochondrial Dysfunction and Energy Deficiency in Alzheimer's Disease. Mitochondrion. 2007;7(5):297-310. PubMed PMID: 17625988.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer's disease. AU - Atamna,Hani, AU - Frey,William H,2nd Y1 - 2007/06/13/ PY - 2007/04/26/received PY - 2007/06/06/accepted PY - 2007/7/13/pubmed PY - 2007/11/6/medline PY - 2007/7/13/entrez SP - 297 EP - 310 JF - Mitochondrion JO - Mitochondrion VL - 7 IS - 5 N2 - Several studies have demonstrated aberrations in the Electron Transport Complexes (ETC) and Krebs (TCA) cycle in Alzheimer's disease (AD) brain. Optimal activity of these key metabolic pathways depends on several redox active centers and metabolites including heme, coenzyme Q, iron-sulfur, vitamins, minerals, and micronutrients. Disturbed heme metabolism leads to increased aberrations in the ETC (loss of complex IV), dimerization of APP, free radical production, markers of oxidative damage, and ultimately cell death all of which represent key cytopathologies in AD. The mechanism of mitochondrial dysfunction in AD is controversial. The observations that Abeta is found both in the cells and in the mitochondria and that Abeta binds with heme may provide clues to this mechanism. Mitochondrial Abeta may interfere with key metabolites or metabolic pathways in a manner that overwhelms the mitochondrial mechanisms of repair. Identifying the molecular mechanism for how Abeta interferes with mitochondria and that explains the established key cytopathologies in AD may also suggest molecular targets for therapeutic interventions. Below we review recent studies describing the possible role of Abeta in altered energy production through heme metabolism. We further discuss how protecting mitochondria could confer resistance to oxidative and environmental insults. Therapies targeted at protecting mitochondria may improve the clinical outcome of AD patients. SN - 1567-7249 UR - https://www.unboundmedicine.com/medline/citation/17625988/Mechanisms_of_mitochondrial_dysfunction_and_energy_deficiency_in_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-7249(07)00112-2 DB - PRIME DP - Unbound Medicine ER -