Accelerating neuronal aging in in vitro model brain disorders: a focus on reactive oxygen species

Abstract

In this review, we discuss insights gained through the use of stem cell preparations regarding the modeling of neurological diseases, the need for aging neurons derived from pluripotent stem cells to further advance the study of late-onset adult neurological diseases, and the extent to which mechanisms linked to the mismanagement of reactive oxygen species (ROS). The context of these issues can be revealed using the three disease states of Parkinson’s (PD), Alzheimer’s (AD), and schizophrenia, as considerable insights have been gained into these conditions through the use of stem cells in terms of disease etiologies and the role of oxidative stress. The latter subject is a primary area of interest of our group. After discussing the molecular models of accelerated aging, we highlight the role of ROS for the three diseases explored here. Importantly, we do not seek to provide an extensive account of all genetic mutations for each of the three disorders discussed in this review, but we aim instead to provide a conceptual framework that could maximize the gains from merging the approaches of stem cell microsystems and the study of oxidative stress in disease in order to optimize therapeutics and determine new molecular targets against oxidative stress that spare stem cell proliferation and development.

Effect of black mulberry (Morus nigra) extract treatment on cognitive impairment and oxidative stress status of d-galactose-induced aging mice

“…Oxidative stress and ROS are proposed to be major biochemical manifestations of the aging process and accumulating information suggests that ROS may have an important role for the development of age-related neuronal impairments in brain (Campos et al 2014). As many anti-aging herbs reduce free radical formation and have antioxidant components, using these herbs may positively influence the biological process of aging.…”

“…SOD catalyzes the superoxide anion to hydrogen peroxide and oxygen, and next as electron donor GSH-Px and/or CAT catalyse. These antioxidant enzymes are substantial in fixing memory and learning deficits because there is a strong relation between oxidative stress and cognitive dysfunction (Obrenovich et al 2011;Campos et al 2014). The functions of liver, which is an important organ in the detoxification system, diminish due to structure atrophy in aging.…”

Flavonoid Enhances the Glyoxalase Pathway in Cerebellar Neurons to Retain Cellular Functions

“…OS is a state of stress placed on organism resulting from disequilibrium between production of prooxidant molecules and the ability to neutralize the reactive molecules 4–6 . The glyoxalase pathway is an antioxidant system crucial in defense against reactive dicarbonyl compounds like methylglyoxal (MG) 7 .…”

Induced pluripotent stem cells as a discovery tool for Alzheimer׳s disease

“…Expression of progerin in iPSC-derived fibroblasts and neurons is sufficient to induce age-related markers such as dendrite degeneration, loss of tyrosine-hydroxylase expression, and mitrochondrial enlargement (Miller et al, 2013). The use of cellular stressors including reactive oxygen species and adenosine also has been suggested to induce an “aging” phenotype (Campos et al, 2014). Optimization and refinement of these and other techniques may allow for more complete modeling of late stage disease processes.…”