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Organic Chemicals
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
William J. Rea, Kalpana D. Patel
NMDA receptor function is also strongly regulated by chemical reduction and oxidation, via the “redox modulatory site.”33 Through this site, reductants dramatically enhance NMDA channel activity, whereas oxidants either reverse the effects of reductants or depress native responses. It is generally believed that NMDA receptors are modulated by endogenous redox agents such as glutathione, lipoic acid, and the essential nutrient pyrroloquinoline quinone. Src kinase enhances NMDA receptor currents.34 Reelin modulates NMDA function through Src family kinases and DAB1,35 significantly enhancing LTP in the hippocampus. CDK5 regulates the amount of NR2B-containing NMDA receptors on the synaptic membrane, thus affecting synaptic plasticity.36,37
Effects of pyrethroids on the cerebellum and related mechanisms: a narrative review
Published in Critical Reviews in Toxicology, 2023
Fei Hao, Ye Bu, Shasha Huang, Wanqi Li, Huiwen Feng, Yuan Wang
Recently, it has been suggested that DM may exert its neurotoxic effects through intracellular accumulation and low release of the reelin protein (Kumar et al. 2013). Reelin is an extracellular matrix molecule that supports the normal development of the CNS, including hippocampus, cerebellum and cortex. In the cerebellum, reelin participates in arranging Purkinje cell monolayers, Bergman glial fibers and facilitating granule cell migration. Reelin protein deficiency in DM-treated animals may lead to certain structural abnormalities that could directly impact the functional performance of the cerebellum. It included impaired migration of granule cells and Purkinje cells, inhibition of neuronal outgrowth, reduced density of dendritic spines and decreased rotational movements (Zhao et al. 1995). Reelin signaling involves several factors, including the lipoprotein receptor lipoprotein E receptor 2 (ApoER2), the very low-density lipoprotein receptor (VLDLR) and adaptor protein Dab1 (Dab1). Reelin can bind to the ApoER2 and VLDLR, leading to phosphorylation of Dab1. Therefore, it is hypothesized that DM may cause cerebellar dysfunction through the reelin signaling pathway.
Proteomic examination of the neuroglial secretome: lessons for the clinic
Published in Expert Review of Proteomics, 2020
Jong-Heon Kim, Ruqayya Afridi, Won-Ha Lee, Kyoungho Suk
Raabe et al. identified the secretion of neuregulins (NRGs) from neonatal oligodendrocytes obtained from rat pups [74]. The study confirmed the presence of NRGs in conditioned medium obtained from neonatal oligodendrocyte culture through western blotting. The secretion of NRGs from oligodendrocytes implies the regulation of their own differentiation as NRGs are responsible for the differentiation of cells. Another study identified the secretion of reelin from oligodendrocytes through microarray analysis of oligodendrocyte conditioned medium [73]. The study also identified several other proteins such as disabled homolog 1 (Dab1) and very low-density lipoprotein receptor (Vldlr). In the brain, reelin plays an important role in the migration and positioning of neuronal cells during development, and the release of reelin from oligodendrocytes implies the possible role of these cells in brain development. A recent report identified previously unappreciated proteins secreted from human oligodendrocytes using mRNA sequencing and cytokine array [72]. Human neural stem cell-derived oligodendrocytes induced by a retroviral vector encoding the Olig2 transcription factor were employed in the study [72]. The study identified several important classes of proteins such as chemokines and growth factors. Although extensive insights into oligodendrocyte-secreted proteins are still required, the reported literature highlights the potential role of oligodendrocytes in brain development and physiology. These studies are also helpful to understand the impact of pathological alterations in microenvironment on the oligodendrocyte secretome and the consequent outcomes.
Understanding SOCS protein specificity
Published in Growth Factors, 2018
Edmond M. Linossi, Dale J. Calleja, Sandra E. Nicholson
The most definitive evidence for functional redundancy comes from the compound deletion of Socs6 and Socs7, which surprisingly leads to an early lethality, despite deletion of the individual genes having no impact on viability (Lawrenson et al., 2017). The lethality is attributed to deregulated cortical neuron migration as a consequence of enhanced Dab1 levels and phosphorylation downstream of Reelin activation (Lawrenson et al., 2017). The loss of either SOCS6 or SOCS7 alone resulted in milder defects in cortical neuron layering (Lawrenson et al., 2017; Simo & Cooper 2013). Thus, SOCS6 and SOCS7 appear to converge on Dab1 during neuronal development to regulate Reelin signalling (Lawrenson et al., 2017).