Modulating Mitochondrial Dynamics Mitigates Cognitive Impairment in Rats with Myocardial Infarction

Current Neuropharmacology, Journal Year: 2024, Volume and Issue: 22(10), P. 1749 - 1760

Published: April 26, 2024

Background: We have previously demonstrated that oxidative stress and brain mitochondrial dysfunction are key mediators of pathology during myocardial infarction (MI). Objective: To investigate the beneficial effects dynamic modulators, including fission inhibitor (Mdivi-1) fusion promotor (M1), on cognitive function molecular signaling in MI rats comparison with effect enalapril. Methods: Male were assigned to either sham or operation. In group, an ejection Fraction less than 50% included, then they received one following treatments for 5 weeks: vehicle, enalapril, Mdivi-1, M1. Cognitive was tested, brains used study. Results: exhibited cardiac systemic stress. impairment found rats, along dendritic spine loss, blood-brain barrier (BBB) breakdown, dysfunction, decreased increased glycolysis metabolism, without alteration APP, BACE-1, Tau p-Tau proteins. Treatment M1, enalapril equally improved rats. All stress, restored metabolism. Brain recovered only Mdivi-1-treated group. Conclusion: Mitochondrial dynamics modulators through a reduction enhancement addition, this

Language: Английский

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Glycolytic dysregulation in Alzheimer’s disease: unveiling new avenues for understanding pathogenesis and improving therapy

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(8), P. 2264 - 2278

Published: July 29, 2024

Alzheimer’s disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence curative treatments. The current therapeutic strategies, primarily based on cholinesterase inhibitors N-methyl-D-aspartate receptor antagonists, offer limited symptomatic relief without halting progression, highlighting an urgent need for novel research directions that address key mechanisms underlying disease. Recent studies have provided insights into critical role glycolysis, fundamental energy metabolism pathway in brain, pathogenesis Alterations glycolytic processes within neurons glial cells, including microglia, astrocytes, oligodendrocytes, been identified as contributors pathological landscape Glycolytic changes impact neuronal function, thus offering promising targets intervention. purpose this review is consolidate knowledge modifications glycolysis associated with explore by which these abnormalities contribute onset progression. Comprehensive focus pathways through dysfunction influences pathology should provide potential strategies pave way groundbreaking treatments, emphasizing importance understanding metabolic quest clarification management

Language: Английский

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Brain Metabolism in Health and Neurodegeneration: The Interplay Among Neurons and Astrocytes

Cells, Journal Year: 2024, Volume and Issue: 13(20), P. 1714 - 1714

Published: Oct. 17, 2024

The regulation of energy in the brain has garnered substantial attention recent years due to its significant implications various disorders and aging. brain's metabolism is a dynamic tightly regulated network that balances demand supply by engaging complementary molecular pathways. crosstalk among these pathways enables system switch preferred fuel source based on substrate availability, activity levels, cell state-related factors such as redox balance. Brain production relies multi-cellular cooperation continuously supplied from blood limited internal stores. Astrocytes, which interface with neurons vessels, play crucial role coordinating metabolic activity, their dysfunction can have detrimental effects health. This review characterizes major substrates (glucose, lactate, glycogen, ketones lipids) astrocyte health, focusing developments field.

Language: Английский

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Metabolic Features of Brain Function with Relevance to Clinical Features of Alzheimer and Parkinson Diseases

Molecules, Journal Year: 2022, Volume and Issue: 27(3), P. 951 - 951

Published: Jan. 30, 2022

Brain metabolism is comprised in Alzheimer’s disease (AD) and Parkinson’s (PD). Since the brain primarily relies on of glucose, ketone bodies, amino acids, aspects these metabolic processes disorders—and particularly how altered are related to oxidative and/or nitrosative stress resulting damaged targets—are reviewed this paper. Greater understanding decreased functions AD PD posited lead potentially important therapeutic strategies address both disorders, which cause relatively long-lasting quality life patients.

Language: Английский

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Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections

Open Biology, Journal Year: 2025, Volume and Issue: 15(2)

Published: Feb. 1, 2025

Glycolysis, present in most organisms, is evolutionarily one of the oldest metabolic pathways. It has great relevance at a physiological level because it responsible for generating ATP cell through conversion glucose into pyruvate and reducing nicotinamide adenine dinucleotide (NADH) (that may be fed electron chain mitochondria to produce additional by oxidative phosphorylation), as well producing intermediates that can serve substrates other processes. Glycolysis takes place 10 consecutive chemical reactions, each which catalysed specific enzyme. Although energy transduction metabolism main function this pathway, involvement virulence, growth, pathogen–host interactions, immunomodulation adaptation environmental conditions are functions attributed pathway. In humans, where glycolysis occurs mainly cytosol, mislocalization some glycolytic enzymes various subcellular locations, alterations their expression regulation, been associated with development progression diseases. review, we describe role pathogenesis diseases clinical interest. addition, potential these targets drug use diagnostic prognostic markers pathologies also discussed.

Language: Английский

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