Redox Homeostasis and Prospects for Therapeutic Targeting in Neurodegenerative Disorders

Abstract

Reactive species, such as those of oxygen, nitrogen, and sulfur, are considered part of normal cellular metabolism and play significant roles that can impact several signaling processes in ways that lead to either cellular sustenance, protection, or damage. Cellular redox processes involve a balance in the production of reactive species (RS) and their removal because redox imbalance may facilitate oxidative damage. Physiologically, redox homeostasis is essential for the maintenance of many cellular processes. RS may serve as signaling molecules or cause oxidative cellular damage depending on the delicate equilibrium between RS production and their efficient removal through the use of enzymatic or nonenzymatic cellular mechanisms. Moreover, accumulating evidence suggests that redox imbalance plays a significant role in the progression of several neurodegenerative diseases. For example, studies have shown that redox imbalance in the brain mediates neurodegeneration and alters normal cytoprotective responses to stress. Therefore, this review describes redox homeostasis in neurodegenerative diseases with a focus on Alzheimer’s and Parkinson’s disease. A clearer understanding of the redox-regulated processes in neurodegenerative disorders may afford opportunities for newer therapeutic strategies.

The neuroprotection of hyperoside in MPP+/MPTP -induced Parkinson’s disease model

“…PD is a slowly progressive neurodegenerative disease characterized by loss of dopaminergic neurons in the SN [1,2]. The etiology and pathology of PD are unclear; however, accumulated evidence strongly viewed oxidative stress as a substantial role underlying the loss of DA neurons in PD pathogenesis [29][30][31]. First of all, oxidative stress (ROS accumulation, increased MDA production, decreased GSH production, etc.)…”

“…First of all, oxidative stress (ROS accumulation, increased MDA production, decreased GSH production, etc.) can result in an impairment of cellular structures, such as ROS production would likely disturb the mitochondrial electron transfer chain (ETC), which is elevated in SN pigmented neurons in PDaffected brains [29,30]. Furthermore, overproduction of reactive oxygen species can trigger DNA spontaneous mutations in neuronal cells and thus enhance the risk of neuronal cells suffering from dysfunction [30].…”

Physical Activity vs. Redox Balance in the Brain: Brain Health, Aging and Diseases

“…The brain is an organ sensitive to oxidative stress due to its oxygen-demanding metabolism, relatively weak enzymatic antioxidant defense and high levels of oxidizable substrates, as well as catalytic transition metals, including copper and iron, characteristic of some brain regions [ 26 , 27 ]. It should be considered that the brain consumes almost ten times more oxygen and glucose than other tissues, having a high demand for adenosine triphosphate (ATP).…”

“…Increased oxidative stress in the mitochondria of dopaminergic neurons is believed to participate in the pathogenesis of Parkinson’s disease (PD) [ 28 , 29 ]. Analogous pathological processes, associated with mitochondrial dysfunctions resulting from the excess production of ROS, have been found to play a detrimental role in Alzheimer’s disease (AD), characterized by neuronal degradation in brain regions that control memory and cognitive and emotional functions [ 26 , 30 , 31 ]. The age-associated loss of mitochondrial functions is supposed to affect the expression and processing of amyloid precursor protein (APP), producing amyloid beta oligomers, which accumulate as plaques in AD [ 31 ].…”

Factors Associated with Urinary 1-Hydroxypyrene and Malondialdehyde among Adults near a Petrochemical Factory: Implications for Sex and Lifestyle Modification

“…Reactive oxygen species (ROS), such as oxygen, nitrogen, and sulfur, are highly reactive derivatives of oxygen metabolism and considered part of normal cellular metabolism. ROS plays a significant role in several signaling processes and can induce cellular damage or protection [18]. Oxidation metabolites are also known as oxidative stress biomarkers.…”