Principles and Therapeutic Relevance for Targeting Mitochondria in Aging and Neurodegenerative Diseases

Gaetano      Serviddio; Antonino      Davide Romano; Tommaso      Cassano; Francesco      Bellanti; Emanuele      Altomare; Gianluigi      Vendemiale

Abstract

Aging is a physiologic state in which a progressive decline of organ functions may be accompanied by developing age-related diseases and neurodegenerative diseases. The causes of such conditions remain unknown, being probably related to a multifactor process. To date, the Free Radical and Mitochondrial theories seem to be the two most prominent that could explain both how and why aged people develop certain disorders, providing a rationale for treatment. Several reports demonstrate that mitochondria play a key role in aging and some neurodegenerative diseases. Damaged mitochondria produce increased amounts of Reactive Oxygen Species (ROS), leading, in turn, to progressive augmentation in damage. Dysfunctional mitochondria enhance susceptibility to cell death. Indeed, at cell level mitochondria act as an energetic hub determining cell final fate through caspase-dependent apoptosis. Thus, if aging results from oxidative stress, it may be corrected by environmental, nutritional and pharmacological strategies. In this review we summarize the role of mitochondria dysfunction occurring in aging and neurodegenerative disease, describing novel mitochondria-targeted therapy approach and the new selective molecules and nanocarriers technology as potentially effective in targeting mitochondrial dysfunction.

Keywords: Oxidative stress, aging, mitochondria, ROS, redox signaling pathways, Alzheimer Disease, Parkinson Disease, Vascular Dementia, mitochondrial-targeted therapy, mitophagy