The role of the host microbiome in autism and neurodegenerative disorders and effect of epigenetic procedures in the brain functions

2021 ◽  
Author(s):  
Bahman Yousefi ◽  
Parviz Kokhaei ◽  
Fatemeh Mehranfar ◽  
Aisa Bahar ◽  
Anna Abdolshahi ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Brain Functions ◽  
The Brain

scholarly journals GSK3α: An Important Paralog in Neurodegenerative Disorders and Cancer

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1683
Author(s):  
Octavio Silva-García ◽  
Ricarda Cortés-Vieyra ◽  
Francisco N. Mendoza-Ambrosio ◽  
Guillermo Ramírez-Galicia ◽  
Víctor M. Baizabal-Aguirre
Keyword(s):  
Neurodegenerative Disorders ◽  
Glycogen Synthase ◽  
Similar Efficacy ◽  
Glycogen Synthase Kinase 3 ◽  
Brain Functions ◽  
Chemical Inhibitors ◽  
Simultaneous Inhibition ◽  
The Brain

The biological activity of the enzyme glycogen synthase kinase-3 (GSK3) is fulfilled by two paralogs named GSK3α and GSK3β, which possess both redundancy and specific functions. The upregulated activity of these proteins is linked to the development of disorders such as neurodegenerative disorders (ND) and cancer. Although various chemical inhibitors of these enzymes restore the brain functions in models of ND such as Alzheimer’s disease (AD), and reduce the proliferation and survival of cancer cells, the particular contribution of each paralog to these effects remains unclear as these molecules downregulate the activity of both paralogs with a similar efficacy. Moreover, given that GSK3 paralogs phosphorylate more than 100 substrates, the simultaneous inhibition of both enzymes has detrimental effects during long-term inhibition. Although the GSK3β kinase function has usually been taken as the global GSK3 activity, in the last few years, a growing interest in the study of GSK3α has emerged because several studies have recognized it as the main GSK3 paralog involved in a variety of diseases. This review summarizes the current biological evidence on the role of GSK3α in AD and various types of cancer. We also provide a discussion on some strategies that may lead to the design of the paralog-specific inhibition of GSK3α.

Role of Flavonoids in Neurodegenerative Disorders with Special Emphasis on Tangeritin

2019 ◽  
Vol 18 (8) ◽  
pp. 581-597 ◽  
Author(s):  
Ambreen Fatima ◽  
Yasir Hasan Siddique
Keyword(s):  
Medicinal Plants ◽  
Mechanism Of Action ◽  
Neurodegenerative Disorders ◽  
Treatment Strategies ◽  
Dietary Supplementation ◽  
Plant Polyphenols ◽  
Promising Candidate ◽  
Naturally Occurring ◽  
The Brain

Flavonoids are naturally occurring plant polyphenols found universally in all fruits, vegetables and medicinal plants. They have emerged as a promising candidate in the formulation of treatment strategies for various neurodegenerative disorders. The use of flavonoid rich plant extracts and food in dietary supplementation have shown favourable outcomes. The present review describes the types, properties and metabolism of flavonoids. Neuroprotective role of various flavonoids and the possible mechanism of action in the brain against the neurodegeneration have been described in detail with special emphasis on the tangeritin.

scholarly journals The Role of Dietary Antioxidants in the Pathogenesis of Neurodegenerative Diseases and Their Impact on Cerebral Oxidoreductive Balance

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 435 ◽  
Author(s):  
Anna Winiarska-Mieczan ◽  
Ewa Baranowska-Wójcik ◽  
Małgorzata Kwiecień ◽  
Eugeniusz R. Grela ◽  
Dominik Szwajgier ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Negative Impact ◽  
Functional Disorders ◽  
Brain Functions ◽  
Diet Supplements ◽  
The Impact ◽  
The Brain ◽  
All Diseases

Neurodegenerative diseases are progressive diseases of the nervous system that lead to neuron loss or functional disorders. Neurodegenerative diseases require long-term, sometimes life-long pharmacological treatment, which increases the risk of adverse effects and a negative impact of pharmaceuticals on the patients’ general condition. One of the main problems related to the treatment of this type of condition is the limited ability to deliver drugs to the brain due to their poor solubility, low bioavailability, and the effects of the blood-brain barrier. Given the above, one of the main objectives of contemporary scientific research focuses on the prevention of neurodegenerative diseases. As disorders related to the competence of the antioxidative system are a marker in all diseases of this type, the primary prophylactics should entail the use of exogenous antioxidants, particularly ones that can be used over extended periods, regardless of the patient’s age, and that are easily available, e.g., as part of a diet or as diet supplements. The paper analyzes the significance of the oxidoreductive balance in the pathogenesis of neurodegenerative diseases. Based on information published globally in the last 10 years, an analysis is also provided with regard to the impact of exogenous antioxidants on brain functions with respect to the prevention of this type of diseases.

scholarly journals The role of nucleotides in the neuron-glia communication responsible for the brain functions

2007 ◽  
Vol 102 (5) ◽  
pp. 1447-1458 ◽  
Author(s):  
Kazuhide Inoue ◽  
Schuichi Koizumi ◽  
Makoto Tsuda
Keyword(s):  
Brain Functions ◽  
The Brain

scholarly journals Wnt5a Increases the Glycolytic Rate and the Activity of the Pentose Phosphate Pathway in Cortical Neurons

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Pedro Cisternas ◽  
Paulina Salazar ◽  
Carmen Silva-Álvarez ◽  
L. Felipe Barros ◽  
Nibaldo C. Inestrosa
Keyword(s):  
Glucose Metabolism ◽  
Wnt Signaling ◽  
Pentose Phosphate Pathway ◽  
Neurodegenerative Disorders ◽  
Metabolic Flux ◽  
High Energy ◽  
Pentose Phosphate ◽  
The Brain ◽  
Glycolytic Rate

In the last few years, several reports have proposed that Wnt signaling is a general metabolic regulator, suggesting a role for this pathway in the control of metabolic flux. Wnt signaling is critical for several neuronal functions, but little is known about the correlation between this pathway and energy metabolism. The brain has a high demand for glucose, which is mainly used for energy production. Neurons use energy for highly specific processes that require a high energy level, such as maintaining the electrical potential and synthesizing neurotransmitters. Moreover, an important metabolic impairment has been described in all neurodegenerative disorders. Despite the key role of glucose metabolism in the brain, little is known about the cellular pathways involved in regulating this process. We report here that Wnt5a induces an increase in glucose uptake and glycolytic rate and an increase in the activity of the pentose phosphate pathway; the effects of Wnt5a require the intracellular generation of nitric oxide. Our data suggest that Wnt signaling stimulates neuronal glucose metabolism, an effect that could be important for the reported neuroprotective role of Wnt signaling in neurodegenerative disorders.

scholarly journals Regulation of neuronal mRNA splicing and Tau isoform ratio by ATXN3 through deubiquitylation of splicing factors

2019 ◽  
Author(s):  
Andreia Neves-Carvalho ◽  
Sara Duarte-Silva ◽  
Joana Silva ◽  
Bruno Almeida ◽  
Sasja Heetveld ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Rna Metabolism ◽  
Mrna Splicing ◽  
Splicing Factors ◽  
Loss Of Function ◽  
Relevant Role ◽  
The Brain ◽  
Precise Role ◽  
Exon 10

ABSTRACTThe ubiquitylation/deubiquitylation balance in cells is maintained by Deubiquitylating enzymes, including ATXN3. The precise role of this protein, mutated in SCA3, remains elusive, as few substrates for its deubiquitylating activity were identified. Therefore, we characterized the ubiquitome of neuronal cells lacking ATXN3, and found altered polyubiquitylation in a large proportion of proteins involved in RNA metabolism, including splicing factors. Using transcriptomic analysis and reporter minigenes we confirmed that splicing was globally altered in these cells. Among the targets with altered splicing was SRSF7 (9G8), a key regulator of MAPT (Tau) exon 10 splicing. Loss-of-function of ATXN3 led to a deregulation of MAPT exon 10 splicing resulting in a decreased 4R/3R-Tau ratio. Similar alterations were found in the brain of a SCA3 mouse and humans, pointing to a relevant role of this mechanism in SCA3, and establishing a previously unsuspected link between two key proteins involved in different neurodegenerative disorders.

scholarly journals Glycogen Synthase Kinase-3β: A Mediator of Inflammation in Alzheimer's Disease?

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Jari Koistinaho ◽  
Tarja Malm ◽  
Gundars Goldsteins
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Immune Defense ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Normal Brain ◽  
Brain Functions ◽  
The Brain

Proliferation and activation of microglial cells is a neuropathological characteristic of brain injury and neurodegeneration, including Alzheimer's disease. Microglia act as the first and main form of immune defense in the nervous system. While the primary function of microglia is to survey and maintain the cellular environment optimal for neurons in the brain parenchyma by actively scavenging the brain for damaged brain cells and foreign proteins or particles, sustained activation of microglia may result in high production of proinflammatory mediators that disturb normal brain functions and even cause neuronal injury. Glycogen synthase kinase-3βhas been recently identified as a major regulator of immune system and mediates inflammatory responses in microglia. Glycogen synthase kinase-3βhas been extensively investigated in connection to tau and amyloidβtoxicity, whereas reports on the role of this enzyme in neuroinflammation in Alzheimer's disease are negligible. Here we review and discuss the role of glycogen synthase-3βin immune cells in the context of Alzheimer's disease pathology.

scholarly journals Lead, Manganese, and Methylmercury as Risk Factors for Neurobehavioral Impairment in Advanced Age

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Bernard Weiss
Keyword(s):  
Risk Factors ◽  
Adverse Effects ◽  
Neurodegenerative Disease ◽  
Early Development ◽  
Neurodegenerative Disorders ◽  
Advanced Age ◽  
Metal Contaminants ◽  
Aging Populations ◽  
The Brain

Contamination of the environment by metals is recognized as a threat to health. One of their targets is the brain, and the adverse functional effects they induce are reflected by neurobehavioral assessments. Lead, manganese, and methylmercury are the metal contaminants linked most comprehensively to such disorders. Because many of these adverse effects can appear later in life, clues to the role of metals as risk factors for neurodegenerative disorders should be sought in the exposure histories of aging populations. A review of the available literature offers evidence that all three metals can produce, in advanced age, manifestations of neurobehavioral dysfunction associated with neurodegenerative disease. Among the critical unresolved questions is timing; that is, during which periods of the lifespan, including early development, do environmental exposures lay the foundations for their ultimate effects?

scholarly journals LncRNA UCA1 facilitated cell growth and invasion through the miR-206/CLOCK axis in glioma

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhi Huang ◽  
Xuya Zhao ◽  
Xiaowen Wu ◽  
Lei Xiang ◽  
Yingnan Yuan ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Brain Functions ◽  
Promising Therapeutic Target ◽  
Glioma Growth ◽  
Life Threatening ◽  
The Brain

Abstract Background Glioma is a lethal malignant brain tumor, which affects the brain functions and is life-threatening. LncRNA UCA1 was identified as a pivotal regulator for tumorigenesis of glioma. MiR-206 was discovered to promote tumorigenesis and is critical in the regulation of cell proliferation in glioma. This study will discuss the expression of UCA1 regarding miR-206 and CLOCK, and their integrative effects in the proliferation and cell cycle of glioma cells. Methods qRT-PCR was conducted to measure the mRNA expressions of IgG and Ago2 in cells co-transfected with UCA1, and miR-216 in U251. Bioinformation was analyzed for the prediction of association between UCA1 and miR-206. Transwell migrations assays and invasion assays were utilized to observe the cell invasive ability. Western blot and immunofluorescence imaging were used to examine the protein expressions. In vivo comparisons and observations were also performed to investigate the role of UCA1 in glioma growth. Results LncRNA UCA1 was up-regulated in glioma cell lines and tissues. It elevated cell invasion via the inducing of epithelial-mesenchymal transition. We found that UCA1 can modulate miR-206 expression and serve as an endogenous sponge of miR-206. The EMT-inducer CLOCK was validated as a messenger RNA target of miR-206. At last, we demonstrated that UCA1 exerted the biology function through regulating miR-206 and CLOCK in vivo. Conclusions Overall, the results demonstrated that UCA1/miR-206/CLOCK axis participated in the progressing of glioma and could act as a promising therapeutic target.

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