Document Detail

Mitochondrial dynamics in Alzheimer's disease: opportunities for future treatment strategies.
MedLine Citation:
PMID:  20210366     Owner:  NLM     Status:  MEDLINE    
The complexities that underlie the cognitive impairment and neurodegeneration characteristic of Alzheimer's disease (AD) have yet to be completely understood, although many factors in disease pathogenesis have been identified. Particularly important in disease development seem to be mitochondrial disturbances. As pivotal role players in cellular metabolism, mitochondria are pertinent to cell survival and thus any deviation from their operation is certainly fatal. In this review, we describe how the dynamic balance of mitochondrial fission and fusion in particular is a necessary aspect of cell proliferation and that, as the cell ages, such balance is inevitably compromised to yield a destructive environment in which the cell cannot exist. Evidence for such disturbance is abundant in AD. Specifically, the dynamic balance of fission and fusion in AD is greatly shifted toward fission, and, as a result, affected neurons contain abnormal mitochondria that are unable to meet the metabolic demands of the cell. Moreover, mitochondrial distribution in AD cells is perinuclear, with few metabolic organelles in the distal processes, where they are normally distributed in healthy cells and are needed for exocytosis, ion channel pumps, synaptic function and other activities. AD neurons are thus characterized by increases in reactive oxidative species and decreases in metabolic capability, and, notably, these changes are evident very early in AD progression. We therefore believe that oxidative stress and altered mitochondrial dynamics contribute to the precipitation of AD pathology and thus cognitive decline. These implications provide a window for therapeutic intervention (i.e. mitochondrial protection) that has the potential to significantly deter AD progression if adequately developed. Current treatment strategies under investigation are described in this review.
David J Bonda; Xinglong Wang; George Perry; Mark A Smith; Xiongwei Zhu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Drugs & aging     Volume:  27     ISSN:  1170-229X     ISO Abbreviation:  Drugs Aging     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-09     Completed Date:  2010-06-01     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  9102074     Medline TA:  Drugs Aging     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  181-92     Citation Subset:  IM    
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MeSH Terms
Aging / metabolism*
Alzheimer Disease / physiopathology*
Cell Proliferation
Citric Acid Cycle / physiology
DNA, Mitochondrial / metabolism
Disease Progression
GTP Phosphohydrolases / metabolism
Membrane Proteins / metabolism
Membrane Transport Proteins / metabolism
Microtubule-Associated Proteins / metabolism
Mitochondria / metabolism*
Mitochondrial Proteins / metabolism
Neurons / metabolism
Oxidative Stress / physiology
Grant Support
AG031852/AG/NIA NIH HHS; R01 AG031852/AG/NIA NIH HHS; R01 AG031852-03/AG/NIA NIH HHS
Reg. No./Substance:
0/DNA, Mitochondrial; 0/FIS1 protein, human; 0/Membrane Proteins; 0/Membrane Transport Proteins; 0/Microtubule-Associated Proteins; 0/Mitochondrial Proteins; EC 3.6.1.-/GTP Phosphohydrolases; EC protein, human

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