Emerging role of mitochondria dysfunction in the onset of neurodegenerative diseases

Abstract

Mitochondria play a pivotal role in a number of biochemical processes in the neuron including energy metabolism and ATP production, intracellular Ca2+ homeostasis and cell signalling which are all implicated in the regulation of neuronal excitability. For this reason, it is not surprising that alterations in mitochondrial function have emerged as a hallmark of aging and various age-related neurodegenerative diseases in which a progressive functional decline of mitochondria has been described. The evidence that mitochondria are concentrated in synapses, together with the observation that synaptic dysfunction identifies an early forerunner of a later neurodegeneration, strongly suggests that significant alterations to synaptic mitochondrial localization, number, morphology, or function can be detrimental to synaptic transmission and might characterize the early stages of many neurological diseases. Thus, the characterization of both molecular players and pathway involved in mitochondria dysfunction will provide new chances to identify pharmacological target for new mitochondria-based drugs aimed at interrupting or slowing down pathological processes and/or ameliorating symptoms of neurological disorders. In this review we provide a current view on the role of mitochondria for neuronal function and how mitochondrial functions impinge on neurological diseases.