Oxidative Stress in Neurodegenerative Diseases: From a Mitochondrial Point of View

Abstract

Age is the main risk factor for a number of human diseases, including neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, which increasing numbers of elderly individuals suffer. These pathological conditions are characterized by progressive loss of neuron cells, compromised motor or cognitive functions, and accumulation of abnormally aggregated proteins. Mitochondrial dysfunction is one of the main features of the aging process, particularly in organs requiring a high-energy source such as the heart, muscles, brain, or liver. Neurons rely almost exclusively on the mitochondria, which produce the energy required for most of the cellular processes, including synaptic plasticity and neurotransmitter synthesis. The brain is particularly vulnerable to oxidative stress and damage, because of its high oxygen consumption, low antioxidant defenses, and high content of polyunsaturated fats very prone to be oxidized. Thus, it is not surprising the importance of protecting systems, including antioxidant defenses, to maintain neuronal integrity and survival. Here, we review the role of mitochondrial oxidative stress in the aging process, with a specific focus on neurodegenerative diseases. Understanding the molecular mechanisms involving mitochondria and oxidative stress in the aging and neurodegeneration may help to identify new strategies for improving the health and extending lifespan.

Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases

“…Various types of biological processes have been implicated in the progression and pathogenesis of neurodegenerative diseases, including oxidative stress, neuroinflammation, excitotoxicity, mitochondrial dysfunction, and apoptosis [8][9][10][11][12][13][14][15][16] (refer Figure 1).…”

The Role of Dietary Antioxidants in the Pathogenesis of Neurodegenerative Diseases and Their Impact on Cerebral Oxidoreductive Balance

“…Such interactions may lead to single or double ruptures in the DNA, the latter being particularly toxic for a cell and capable of directly triggering cell death; they can also lead to the emergence of networking bonds or modifications to nitrogen bases [48,49]. Furthermore, attention has been drawn to damaged mitochondrial DNA (mtDNA), which may be a significant element in the etiology of many diseases and senile conditions [50]. Hydrogen peroxide and superoxide anion radical initiate DNA damage by interacting with ions of organic compounds containing metals (iron, copper) via Fenton's reaction, which leads to the formation of •OH [10].…”

“…Mitochondrial DNA is particularly susceptible to the effects of ROS mainly because mitochondria are responsible for the consumption of approximately 90% of all oxygen processed by the organism, with 1-2% of the metabolized oxygen being converted into free radical forms. Furthermore, mtDNA molecules are located in the vicinity of the inner mitochondrial membrane whose electron transport system is conducive to ROS production; mtDNA is not bound to histone proteins, and mitochondrial genes are less protected by the DNA repair system when compared to nuclear DNA [46,50]. Other common changes to mtDNA include deletions; in human fibroblasts exposed to ROS one of the most common deletions, mtDNA 4977 , is accumulated [53].…”

Neuroprotective Effects of Necrostatin-1 Against Oxidative Stress–Induced Cell Damage: an Involvement of Cathepsin D Inhibition

“…With the aim to extend a neuroprotective portfolio of Nec-1, in the present study, we tested the hypothesis that this compound protects human neuroblastoma SH-SY5Y cells against the hydrogen peroxide (H 2 O 2 )-and 6-hydroxydopamine (6-OHDA)-induced cell damage. The used experimental models are widely accepted as cellular models of PD, where elevated oxidative stress is a significant contributor to neuropathology of this disease (Agholme et al 2010;Castelli et al 2019;Cenini et al 2019;Cheung et al 2009;Miloso et al 2004). Based on our previous experiences, where neuronal differentiation of SH-SY5Y cells could mask or limit a protective effect of the tested agents (Jantas et al 2014b(Jantas et al , 2015b, we hypothesized that Nec-1 will afford a greater protection to undifferentiated (UN-SH-SY5Y) cells in comparison with retinoic acid (RA)-differentiated (RA-SH-SY5Y) ones.…”