Treating neurodegeneration by modifying mitochondria: potential solutions to a "complex" problem.
Mitochondria function differently in aged brains than they do in young brains. Consistently reported changes include reduced electron transport chain (ETC) enzyme activities, reduced phosphorylation of ADP, and increased reactive oxygen species (ROS) production. Various neurodegenerative diseases are also associated with changes in mitochondrial function, and these changes both recapitulate and extend those seen in "normal" aging. Unfortunately, attempts to treat neurodegenerative diseases by treating mitochondria-related pathology have thus far minimally impacted affected patients. A better understanding of how mitochondrial function changes in aging and neurodegenerative diseases, though, now suggests new approaches to mitochondrial therapy may prove more efficacious. Increasing ETC capacity, increasing oxidative phosphorylation, or decreasing mitochondrial ROS may yet prove useful for the treatment of brain aging and neurodegenerative diseases, and accomplishing this seems increasingly feasible. This review will discuss the role of mitochondrial function and dysfunction in aging and neurodegenerative diseases, and will focus on potential treatment strategies.
Swerdlow
Russell H
RH
Department of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA. rhs7e@virginia.edu
D001921:Brain / Q000503:physiopathology; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000503:physiopathology* / Q000628:therapy