http://onlinelibrary.wiley.com/doi/10.1002/ana.24014/abstract
DOI: 10.1002/ana.24014
ABSTRACT
Energy
failure from mitochondrial dysfunction is proposed to be a central
mechanism leading to neuronal death in a range of neurodegenerative
diseases. However, energy failure has never been directly demonstrated
in affected neurons in these diseases, nor has it been proved to produce
degeneration in disease models. Therefore, despite considerable
indirect evidence, it is not known if energy failure truly occurs in
susceptible neurons, and if this failure is responsible for their death.
This limited understanding results primarily from a lack of sensitivity
and resolution of available tools and assays and the inherent
limitations of in vitro model systems. Major advances in these
methodologies and approaches should greatly enhance our understanding of
the relationship between energy failure, neuronal dysfunction and
death, and help us to determine if boosting bioenergetic function would
be an effective therapeutic approach. Here we review the current
evidence that energy failure occurs in and contributes to
neurodegenerative disease, and consider new approaches that may allow us
to better address this central issue. ANN NEUROL 2013. © 2013 American
Neurological Association
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