Targeting mitochondrial dysfunction in neurodegenerative disease: Part I.
BACKGROUND
The socioeconomic burden of an aging population has accelerated the urgency of novel therapeutic strategies for neurodegenerative disease. One possible approach is to target mitochondrial dysfunction, which has been implicated in the pathogenesis of numerous neurodegenerative disorders.


METHODS
This review examines the role of mitochondrial defects in aging and neurodegenerative disease, ranging from common diseases such as Alzheimer's and Parkinson's disease to rare familial disorders such as the spinocerebellar ataxias. The review is provided in two parts; in this first part, we discuss the mitochondrial defects that have been most extensively researched: oxidative stress; bioenergetic dysfunction and calcium deregulation.


RESULTS
This review provides a comprehensive examination of mitochondrial defects observed in numerous neurodegenerative disorders, discussing therapies that have reached clinical trials and considering potential novel therapeutic strategies to target mitochondrial dysfunction.


CONCLUSIONS
This is an important area of clinical research, with several novel therapeutics already in clinical trials and many more in preclinical stages. In part II of this review we will focus on possible novel approaches, looking at mitochondrial defects which have more recently been linked to neurodegeneration.
Burchell
Victoria S
VS
UCL Institute of Neurology, Department of Molecular Neuroscience, Queen Square, London WC1N 3BG, UK.
Gandhi
Sonia
S
Deas
Emma
E
Wood
Nicholas W
NW
Abramov
Andrey Y
AY
Plun-Favreau
Hélène
H
D000375:Aging / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000009:adverse effects / Q000502:physiology; D002128:Calcium Metabolism Disorders / Q000188:drug therapy / Q000503:physiopathology; D004734:Energy Metabolism / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D028361:Mitochondrial Diseases / Q000188:drug therapy*; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects
D002118:Calcium