(mentions CMT) Targeting mitochondrial dysfunction in neurodegenerative disease:

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Expert Opin Ther Targets. 2010 Mar 24

Targeting mitochondrial dysfunction in neurodegenerative disease: Part II.

Burchell VS, Gandhi S, Deas E, Wood NW, Abramov AY, Plun-Favreau H.

UCL Institute of Neurology, Department of Molecular Neuroscience, Queen Square,

London WC1N 3BG, UK.

Importance of the field: With improvements in life expectancy over the past

decades, the incidence of neurodegenerative disease has dramatically increased

and new therapeutic strategies are urgently needed. One possible approach is to

target mitochondrial dysfunction, which has been implicated in the pathogenesis

of numerous neurodegenerative disorders.

Areas covered in this review: This review examines the role of mitochondrial

dysfunction in neurodegeneration, drawing examples from common diseases such as

Alzheimer's disease and rarer familial disorders such as Charcot-Marie-Tooth.

The review is provided in two parts.

In part I we discussed the mitochondrial defects which have been most

extensively researched (oxidative stress, bioenergetic dysfunction, calcium

mishandling). We focus now on those defects which have more recently been

implicated in neurodegeneration; in mitochondrial fusion/fission, protein

import, protein quality control, kinase signalling and opening of the

permeability transition pore.

What the reader will gain: An examination of mitochondrial defects observed in

neurodegeneration, and existing and possible future therapies to target these

defects.

Take home message: The mitochondrially-targeted therapeutics that have reached

clinical trials so far have produced encouraging but largely inconclusive

results. Increasing understanding of mitochondrial dysfunction has, however, led

to preclinical work focusing on novel approaches, which has generated exciting

preliminary data.