Oxidative-Signaling in Neural Stem Cell-Mediated Plasticity: Implications for Neurodegenerative Diseases

Abstract

The adult mammalian brain is capable of generating new neurons from existing neural stem cells (NSCs) in a process called adult neurogenesis. This process, which is critical for sustaining cognition and mental health in the mature brain, can be severely hampered with ageing and different neurological disorders. Recently, it is believed that the beneficial effects of NSCs in the injured brain relies not only on their potential to differentiate and integrate into the preexisting network, but also on their secreted molecules. In fact, further insight into adult NSC function is being gained, pointing to these cells as powerful endogenous “factories” that produce and secrete a large range of bioactive molecules with therapeutic properties. Beyond anti-inflammatory, neurogenic and neurotrophic effects, NSC-derived secretome has antioxidant proprieties that prevent mitochondrial dysfunction and rescue recipient cells from oxidative damage. This is particularly important in neurodegenerative contexts, where oxidative stress and mitochondrial dysfunction play a significant role. In this review, we discuss the current knowledge and the therapeutic opportunities of NSC secretome for neurodegenerative diseases with a particular focus on mitochondria and its oxidative state.

Stem Cells and the Microenvironment: Reciprocity with Asymmetry in Regenerative Medicine

“…stress (Santos et al 2021). On the other hand, Aβ peptides (e.g., Aβ42 peptides) could favor neurogenesis of neural stem cells by promoting the migratory potential of neural stem cells toward inflamed lesions in animal brains (López-Toledano and Shelanski 2004).…”

Targeting MicroRNA-144/451-AKT-GSK3β Axis Affects the Proliferation and Differentiation of Radial Glial Cells in the Mouse Hippocampal Dentate Gyrus

“…54,55 The proliferation and migration of neural precursor cells can be inhibited by reactive oxygen species (ROS). 56,57 To aid the removal of ROS, mammals possess a set of antioxidant defense systems that are composed of various functional components, including nonenzymatic and enzymatic antioxidants. There are multiple antioxidant enzymes, such as SODs, catalase, and GPXs, which play a vital role in neurogenesis in the hippocampal DG region throughout neurodevelopment.…”

“…Melatonin is widely accepted as nature’s defense against ROS, and it improves the genomic function and the expression of antioxidant enzymes, including SOD, GPX, and catalase. , Neural tissue is especially vulnerable to oxidative damage induced by aging, brain injury, and neurological diseases. , The proliferation and migration of neural precursor cells can be inhibited by reactive oxygen species (ROS). , To aid the removal of ROS, mammals possess a set of antioxidant defense systems that are composed of various functional components, including nonenzymatic and enzymatic antioxidants. There are multiple antioxidant enzymes, such as SODs, catalase, and GPXs, which play a vital role in neurogenesis in the hippocampal DG region throughout neurodevelopment. , We previously reported that miR-451 could protect erythroid cells from damage related to oxidative stress by repressing the expression of 14-3-3zeta .…”

Mechanism of spinal cord injury regeneration and the effect of human neural stem cells-secretome treatment in rat model

“…Kim et al [ 12 ] stated that adipose derived stem cell-secretome can provide anti-free-radical effects and reduce oxidative stress with the expression of F2-Isoprostane. Honmou et al [ 13 ] also stated that mononuclear stem cell secretome in SCI inhibited microvascular obstruction and thrombosis, promoted vasodilation, immunomodulation, and neuroprotection, while Santos et al [ 14 ] and Yang et al [ 15 ] stated that NSC-secretome in SCI stimulated the transformation of phenotype M1 to phenotype M2 of macrophages, microglia, and astrocytes through PgE2, IL-10, TGF-β, proliferator-activated receptor gamma[ 14 , 15 ]. Macrophage M2 secreted anti-inflammatory cytokines IL-4, IL-10, TGF-β, and hepatocyte growth factor, whereas macrophage M1 secreted pro-inflammatory cytokines IL-1, IL-6, IL-8, TNF-α, MMP9, and F2-Isophostane[ 14 , 15 ].…”