Metabolic Dysregulation Contributes to the Progression of Alzheimer’s Disease

Frontiers in Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Nov. 5, 2020

Alzheimer's disease (AD) is an incurable neurodegenerative disease. Numerous studies have demonstrated a critical role for dysregulated glucose metabolism in its pathogenesis. In this review, we summarize metabolic alterations aging brain and AD-related deficits associated with dysregulation, glycolysis dysfunction, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS) deficits, pentose phosphate pathway impairment. Additionally, discuss recent treatment strategies targeting defects AD, including their limitations, effort to encourage the development of novel therapeutic strategies.

Language: Английский

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Neuroinflammation in Schizophrenia: The Key Role of the WNT/β-Catenin Pathway

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2810 - 2810

Published: March 4, 2022

Schizophrenia is a very complex syndrome involving widespread brain multi-dysconnectivity. marked by cognitive, behavioral, and emotional dysregulations. Recent studies suggest that inflammation in the central nervous system (CNS) immune dysfunction could have role pathogenesis of schizophrenia. This hypothesis supported immunogenetic evidence, higher incidence rate autoimmune diseases patients with The dysregulation WNT/β-catenin pathway associated involvement neuroinflammation Several shown there vicious positive interplay operating between oxidative stress. modulated WNT/β-catenin, which interacts NF-kB pathway; inflammatory factors (including IL-6, IL-8, TNF-α); stress such as glutamate; dopamine. Neuroinflammation increased levels PPARγ. In schizophrenia, expression PPAR-γ increased, whereas PPARα are downregulated. suggests metabolic-inflammatory imbalance occurs this disorder. Thus, research’s triptych be novel therapeutic approach to counteract both

Language: Английский

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TGF-β in fibrosis by acting as a conductor for contractile properties of myofibroblasts

Cell & Bioscience, Journal Year: 2019, Volume and Issue: 9(1)

Published: Dec. 1, 2019

Abstract Myofibroblasts are non-muscle contractile cells that play a key physiologically role in organs such as the stem villi of human placenta during physiological pregnancy. They able to contract and relax response changes volume intervillous chamber. have also been observed several diseases involved wound healing fibrotic processes affecting organs, liver, lungs, kidneys heart. During process, tissue retraction rather than contraction is correlated with collagen synthesis extracellular matrix, leading irreversible fibrosis and, finally, apoptosis myofibroblasts. The molecular motor myofibroblasts type IIA B myosin (NMMIIA NMMIIB). Fibroblast differentiation into largely governed by transforming growth factor-β1 (TGF-β1). This system controls canonical WNT/β-catenin pathway positive manner, PPARγ negative manner. promotes fibrosis, while prevents it. review focuses on properties conductor, TGF-β1, which together control opposing interplay between pathway.

Language: Английский

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Targeting the Canonical WNT/β-Catenin Pathway in Cancer Treatment Using Non-Steroidal Anti-Inflammatory Drugs

Cells, Journal Year: 2019, Volume and Issue: 8(7), P. 726 - 726

Published: July 15, 2019

Chronic inflammation and oxidative stress are common co-substantial pathological processes accompanying contributing to cancers. Numerous epidemiological studies have indicated that non-steroidal anti-inflammatory drugs (NSAIDs) could a positive effect on both the prevention of cancer tumor therapy. hypotheses postulated NSAIDs slow growth by acting chronic stress. This review takes closer look at these hypotheses. In process, one major signaling pathways involved is WNT/β-catenin pathway, which appears be upregulated. pathway closely associated with in The administration has been observed help downregulation thus control growth. act as PPARγ agonists. opposing manners. agonists can promote cell cycle arrest, differentiation, apoptosis, reduce inflammation, stress, proliferation, invasion, migration. parallel, dysregulation circadian rhythms (CRs) contributes development through upregulation canonical pathway. By stimulating expression, CRs regulation many key genes. treatment would appear an interesting therapeutic strategy, acts their role regulating activity levels.

Language: Английский

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Curcumin: a therapeutic strategy in cancers by inhibiting the canonical WNT/β-catenin pathway

Journal of Experimental & Clinical Cancer Research, Journal Year: 2019, Volume and Issue: 38(1)

Published: July 22, 2019

Numerous studies have presented that curcumin could a positive effect in the prevention of cancer and then tumor therapy. Several hypotheses highlighted decreases growth invasion by acting on both chronic inflammation oxidative stress. This review focuses interest use therapy WNT/β-catenin pathway to repress In process, one major signaling pathways involved is pathway, which appears be upregulated. Curcumin administration participates downregulation thus, through this action, control. act as PPARγ agonists. The an opposed manner. Chronic inflammation, stress circadian clock disruption are common co-substantial pathological processes accompanying promoting cancers. Circadian related upregulation By stimulating expression, can control clocks regulation many key genes. treatment would thus appear interesting therapeutic strategy, acts their role regulating activity levels.

Language: Английский

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The Key Role of the WNT/β-Catenin Pathway in Metabolic Reprogramming in Cancers under Normoxic Conditions

Cancers, Journal Year: 2021, Volume and Issue: 13(21), P. 5557 - 5557

Published: Nov. 5, 2021

The canonical WNT/β-catenin pathway is upregulated in cancers and plays a major role proliferation, invasion, apoptosis angiogenesis. Nuclear β-catenin accumulation associated with cancer. Hypoxic mechanisms lead to the activation of hypoxia-inducible factor (HIF)-1α, promoting glycolytic energetic metabolism However, HIF-1α degraded by HIF prolyl hydroxylase under normoxia, conditions which can activate HIF-1α. This review therefore focused on interaction between metabolic processes underlying cancer normoxic conditions. WNT stimulates PI3K/Akt pathway, STAT3 transduction target genes (such as c-Myc) activity hypoxia-independent manner. In cancers, stimulation induces many enzymes, turn induce reprogramming, known Warburg effect or aerobic glycolysis, leading lactate overproduction. Wnt/β-catenin gene transactivation via genes, c-Myc cyclin D1, encodes glycolysis including glucose transporter, hexokinase 2, pyruvate kinase M2, dehydrogenase 1 dehydrogenase-A, production. increase production modifications tumor microenvironment growth Moreover, increased overexpression VEGF, key inducer Thus, conditions, overstimulation leads effect, autophagy glutaminolysis, participate growth.

Language: Английский

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Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102480 - 102480

Published: Sept. 3, 2024

Mitochondria functionally degrade as neurons age. Degenerative changes cause inefficient oxidative phosphorylation (OXPHOS) and elevated electron leakage from the transport chain (ETC) promoting increased intramitochondrial generation of damaging reactive oxygen nitrogen species (ROS RNS). The associated progressive accumulation molecular damage causes an increasingly rapid decline in mitochondrial physiology contributing to aging. Melatonin, a multifunctional free radical scavenger indirect antioxidant, is synthesized matrix neurons. Melatonin reduces ETC elevates ATP production; it also detoxifies ROS/RNS via SIRT3/FOXO pathway upregulates activities superoxide dismutase 2 glutathione peroxidase. influences glucose processing by In neurogenerative diseases, often adopt Warburg-type metabolism which excludes pyruvate mitochondria causing reduced acetyl coenzyme A production. Acetyl supports citric acid cycle OXPHOS. Additionally, required co-substrate for arylalkylamine-N-acetyl transferase, rate limits melatonin synthesis; therefore, production diminished cells that experience making more vulnerable stress. Moreover, endogenously produced diminishes during aging, further increasing components. More normal preserved aging with supplementation.

Language: Английский

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Premature cell senescence in human skin: Dual face in chronic acquired pigmentary disorders

Ageing Research Reviews, Journal Year: 2019, Volume and Issue: 57, P. 100981 - 100981

Published: Nov. 14, 2019

Language: Английский

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Parkinson’s Disease: Potential Actions of Lithium by Targeting the WNT/β-Catenin Pathway, Oxidative Stress, Inflammation and Glutamatergic Pathway

Cells, Journal Year: 2021, Volume and Issue: 10(2), P. 230 - 230

Published: Jan. 25, 2021

Parkinson’s disease (PD) is one of the major neurodegenerative diseases (ND) which presents a progressive neurodegeneration characterized by loss dopamine in substantia nigra pars compacta. It well known that oxidative stress, inflammation and glutamatergic pathway play key roles development PD. However, therapies remain uncertain research for new treatment mandatory. This review focuses on potential effects lithium, as therapeutic strategy, PD some presumed mechanisms lithium provides its benefit properties. Lithium medication downregulates GSK-3beta, main inhibitor WNT/β-catenin pathway. The stimulation could be associated with control inflammation, Future prospective clinical trials focus different multiple interactions

Language: Английский

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Interplay of Opposing Effects of the WNT/β-Catenin Pathway and PPARγ and Implications for SARS-CoV2 Treatment

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: April 13, 2021

The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome 2), has quickly reached pandemic proportions. Cytokine profiles observed in COVID-19 patients have revealed increased levels of IL-1β, IL-2, IL-6, and TNF-α NF-κB pathway activity. Recent evidence shown that upregulation WNT/β-catenin is associated with inflammation, resulting a cytokine storm ARDS (acute respire distress syndrome) especially patients. Several studies interacts PPARγ an opposing interplay numerous diseases. Furthermore, recent highlighted interesting role agonists as modulators inflammatory immunomodulatory drugs through targeting SARS-CoV2 infection presents decrease angiotensin-converting enzyme 2 (ACE2) pathway. SARS-Cov2 may invade human organs besides lungs expression ACE2. Evidence fact can increase ACE2 expression, suggesting possible for treatment COVID-19. This review therefore focuses on between canonical potential beneficial this context.

Language: Английский

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