Mitochondrial Changes and Bioenergetics in Neurodegenerative Diseases

Mitochondria are dynamic organelles that are of critical importance for cellular survival and health. Because mitochondria play central roles in energy production and synaptic maintenance, neurons are believed to be particularly vulnerable to mitochondrial dysfunction. The discovery that genetic mutations in genes coding for mitochondrial proteins cause neurodegenerative conditions further hinted at the likelihood that mitochondrial dysfunction is a key pathway of neurodegeneration. Indeed, a wealth of research has identified mitochondrial dysfunction as an early and shared event of all common neurodegenerative diseases, both genetic and sporadic in origin. Specific types of mitochondrial dysfunction that have been observed in most neurodegenerative diseases include bioenergetic failure, increased oxidative stress, mitochondrial DNA mutations, defective calcium handling, impaired mitochondrial dynamics, defective mitophagy, and decreased mitochondrial biogenesis. The search for drugs that successfully target these pathways of mitochondrial dysfunction in neurodegeneration is ongoing.