Impaired function of certain mitochondrial respiratory complexes has long been linked to the pathogenesis of chronic
neurodegenerative disorders such as Parkinson's and Huntington's diseases. Furthermore, genetic alterations of mitochondrial genome or nuclear genes encoding
proteins playing essential roles in maintaining proper mitochondrial function can lead to the development of severe systemic diseases associated with neurodegeneration and
vacuolar myelinopathy. At present, all of these diseases lack effective disease modifying
therapy. Following a brief commemoration of Professor Albert Szent-Györgyi, a Nobel Prize laureate who pioneered in the field of cellular respiration,
antioxidant processes, and the roles of
free radicals in health and disease, the present paper overviews the current knowledge on the involvement of
mitochondrial dysfunction in
central nervous system diseases associated with neurodegeneration including Parkinson's and
Huntington's disease as well as mitochondrial
encephalopathies. The review puts special focus on the involvement and the potential therapeutic relevance of
peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α), a nuclear-encoded master regulator of mitochondrial biogenesis and
antioxidant responses in these disorders, the transcriptional activation of which may hold novel therapeutic value as a more system-based approach aiming to restore mitochondrial functions in neurodegenerative processes.