Oxidative Stress and Mitochondrial Damage in Neurodegenerative Diseases: From Molecular Mechanisms to Targeted Therapies

摘要

A growing body of evidence suggests the alteration of the reduction-oxidation (redox) homeostasis in the brain grown with the increasing of the age. The brain is composed of highly differentiated cells that populate different anatomical regions and requires about 20% of body basal oxygen for its functions [ ]. Thus, it is not surprising that oxidative stress, as well as alterations in brain energy metabolisms, have been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). These neurodegenerative disorders are typically characterized by the progressive loss of neuronal cells and compromised motor or cognitive functions. It has been shown that neuronal cells are particularly vulnerable to oxidative damage due to their high polyunsaturated fatty acid content in membranes, high oxygen consumption, and weak antioxidant defence. Cellular energy is mainly produced via oxidative phosphorylation taking place within mitochondria, which are crucial organelles for numerous cellular processes, such as energy metabolism, calcium homeostasis, lipid biosynthesis, and apoptosis [ , ]. Glucose oxidation is the most relevant source of energy in the brain because of its high rate of ATP generation needed to maintain neuronal energy demands [ ]. Thus, neurons rely almost exclusively on the mitochondria, which produce the energy required for most of the cellular processes, including synaptic plasticity and neurotransmitter synthesis [ ].