China
Africa
Explore chapters and articles related to this topic
Lipidomic Insight into Membrane Remodeling in Aging and Neurodegenerative Diseases
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Long-term inflammation in the brain results in neurofibrillary fibers formed of abnormal tau protein trigger alterations in cytoskeletal stability, axonal transport, and loss of synaptic contacts [72], resulting in more phosphorylated tau (p-tau), axonal blockage and leakage, and ultimately cell death. DHA can decrease the p-tau levels by inhibition of the phosphorylation of tau protein via the c-Jun N-terminal kinase 1 (JNK1) or Akt through glycogen synthase kinase-3β (GSK3β) [78], and can help to stabilize white matter [79]. The activation of the Akt pathway promotes cell survival via inhibition of caspase-3, potentially protecting neurons during metabolic stress. Reelin expression decreases with age and increases with sufficient DHA, and reelin is thought to be involved in the pathogenesis of AD [80]. Both reelin and DHA increase phosphoinositide 3-kinase (PI3K) activity, which activates Akt, which, in turn, inhibits GSK3β. GSK3β inhibits glycogen production and phosphorylates tau, and ultimately it is this poor glucose uptake and storage in combination with tau hyperphosphorylation that likely precipitates AD pathology [81]. Some data suggest that the AD pathophysiology is to some extent mediated by impairment of insulin sensitivity, and in glucose metabolism and utilization, which lead to oxidative stress and inflammation. Accordingly, diabetes patients are more likely to develop dementia [82]. Interestingly, animal and in-vitro studies identify positive effects of DHA on endothelial and glial GLUT1 levels and brain glucose uptake [83,84].
Therapeutic Strategies and Future Research
Published in Mark A. Mentzer, Mild Traumatic Brain Injury, 2020
Apolipoprotein (apo) E is a major genetic risk factor for Alzheimer’s disease (65%–80% of AD patients have one or more apoE4 allele). Perhaps as the allele plays a role in mTBI, the detrimental effects could be modulated by potential therapies (Mahley et al., 2012). The apoE receptor ligand reelin mediates signaling in several molecular pathways and could be an important factor in modulating amyloid and tau pathologies (Krstic et al., 2012). Reelin receptors apoER2 and VLDLR are part of normal synaptic plasticity, learning, and memory (Weeber, 2012). Therapies to slow the rate of decline from tau aggregation for both AD and mTBI are being pursued but none are currently available. Another potential therapy for mTBI and the secondary injury effects is the gamma-secretase inhibitors. Gamma-secretase blocking can reduce motor and cognitive deficits and reduce cell loss following TBI (Burns, 2012).
Antimanic Drugs
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Aman Upaganlawar, Abdulla Sherikar, Chandrashekhar Upasani
Valproic acid acts as novel histone deacetylase (HDAC) inhibitor and regulates gene expression. Histones are the small basic proteins and DNA complex. Histones present as histone acetylases (HATs) and HDACs forms. Acetylation of histones decreased their affinity toward DNA and is a major regulator of gene expression. A discriminating increase of DNA-methyltransferase 1 concentration in GABAergic neurons due to epigenetic hypermethylation of the respective promoters causes downregulation of reelin and GAD expression in cortical interneurons of schizophrenia and bipolar disorder patients. In addition to this valproic acid causes prevention of hypermethylation of reelin promoter which is methionine based mechanism and reelin mRNA downregulation as well as causes the correction of drawbacks of social interaction (Carlos et al., 2006). Valproic acid has antimanic and mood stabilizing effect as that of lithium (Manji et al., 1993). Valproic acid decreases an expression of myristoylated alanine-rich PKC-kinase substrate (MARCKS) protein, increases appearance of the regulatory protein β-cell lymphocyte protein-2 (bcl-2) (Chen et al., 1999c; Manji et al., 1999c), and inhibits glycogen synthase kinase-3b (GSK-3b) as that of lithium (Chen et al., 1999b; Manji et al., 1999b).
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.
The relationship between attention deficit hyperactivity disorder and reelin gene polymorphisms in Turkish population
Published in Psychiatry and Clinical Psychopharmacology, 2018
Bilge Kara, Nilfer Sahin, Murat Kara, Esin Sakalli Cetin, Hatice Topal
Reelin has been reported to have an important role in neurodevelopment by regulating neuronal migration, laminar organization, dendritic arbour, and neurotransmission [23]. Animal studies have shown that non-foliated cerebellum of double knock-out RELN genes caused deficiencies in the lamination of the hippocampus and disorganization in the amigdala [24,25]. Mice with reelin deficiency have shown to have largely inverted cortex layers, which strongly support the idea that reelin is a key regulator in cortical development. In previous animal studies, a more complex model has been shown rather than the cortex laminar formation by reelin in the brain, which was previously thought [24,26].