From Brain to Muscle: The Role of Muscle Tissue in Neurodegenerative Disorders

Biology, Journal Year: 2024, Volume and Issue: 13(9), P. 719 - 719

Published: Sept. 12, 2024

Neurodegenerative diseases (NDs), like amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's (PD), primarily affect the central nervous system, leading to progressive neuronal loss motor cognitive dysfunction. However, recent studies have revealed that muscle tissue also plays a significant role in these diseases. ALS is characterized by severe wasting as result of neuron degeneration, well alterations gene expression, protein aggregation, oxidative stress. Muscle atrophy mitochondrial dysfunction are observed AD, which may exacerbate decline due systemic metabolic dysregulation. PD patients exhibit fiber atrophy, altered composition, α-synuclein aggregation within cells, contributing symptoms progression. Systemic inflammation impaired degradation pathways common among disorders, highlighting key player Understanding muscle-related changes offers potential therapeutic avenues, such targeting function, reducing inflammation, promoting regeneration with exercise pharmacological interventions. This review emphasizes importance considering an integrative approach neurodegenerative research, both peripheral pathological mechanisms, order develop more effective treatments improve patient outcomes.

Language: Английский

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The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 9082 - 9082

Published: Aug. 21, 2024

Kynurenic acid (KYNA) is an antioxidant degradation product of tryptophan that has been shown to have a variety cytoprotective, neuroprotective and neuronal signalling properties. However, mammalian transporters receptors display micromolar binding constants; these are consistent with its typically tissue concentrations but far above serum/plasma concentration (normally tens nanomolar), suggesting large gaps in our knowledge transport mechanisms action, the main influx characterized date equilibrative, not concentrative. In addition, it substrate known anion efflux pump (ABCC4), whose vivo activity largely unknown. Exogeneous addition L-tryptophan or L-kynurenine leads production KYNA also many other co-metabolites (including some such as 3-hydroxy-L-kynurenine quinolinic may be toxic). With exception chestnut honey, exists at relatively low levels natural foodstuffs. bioavailability reasonable, terminal element irreversible reaction most pathways, might added exogenously without disturbing upstream metabolism significantly. Many examples, which we review, show valuable bioactivity. Given above, review potential utility nutraceutical, finding significantly worthy further study development.

Language: Английский

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Osteocalcin and GPR158: linking bone and brain function

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: April 23, 2025

Osteocalcin (OCN), a small protein secreted by osteoblasts, has attracted significant attention for its role as an endocrine factor in regulating the central nervous system (CNS) via bone-brain axis. As critical receptor OCN, G protein-coupled 158 (GPR158) facilitates proliferation, differentiation, and survival of neural cells while directly influencing neurons' structural functional plasticity, thereby modulating cognitive function. Additionally, GPR158 is involved cellular energy metabolism interacts with proteins such regulators signaling 7 (RGS7), broadening understanding OCN’s impact on activity. Notably, displays region- cell type-specific bidirectional effects under certain pathological conditions, tumor development mood regulation, adding complexity to mechanisms action. Although precise biological underlying OCN/GPR158 pathway remain incompletely understood, association neurodegenerative diseases (NDs), including Alzheimer’s disease (AD) Parkinson’s (PD), becoming increasingly evident. Thus, systematic summary CNS regulation NDs will deepen brain function support new therapeutic targets strategies.

Language: Английский

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Muscle‐Derived Small Extracellular Vesicles Mediate Exercise‐Induced Cognitive Protection in Chronic Cerebral Hypoperfusion

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Abstract Physical exercise protects against cognitive impairment caused by chronic cerebral hypoperfusion (CCH). However, the mechanisms through which sends signals from periphery to central nervous system remain incompletely understood. This study demonstrated that promotes secretion of muscle‐derived small extracellular vesicles (sEVs), facilitate interorgan communication between muscle and brain. Systematic delivery sEVs enhances synaptic plasticity alleviated in CCH. Notably, miRNA sequencing reveal miR‐17/20a‐5p as key cargos involved exercise‐induced muscle‐brain crosstalk. Muscle‐derived are also identified primary source swimming‐induced circulating sEVs. Mechanistically, binds DEP‐domain containing mTOR‐interacting protein (DEPTOR) activates mammalian target rapamycin (mTOR) pathway hippocampus. Depletion impairs enhancement function. Moreover, overexpression DEPTOR hippocampus attenuates benefits exercise. Conversely, hippocampus‐specific activation mTOR reverses these effects, highlighting crucial role mediating positive effects Collectively, findings identify myokine with potent on brain, emphasizing therapeutic potential managing impairment.

Language: Английский

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‘Exerkines’: A Comprehensive Term for the Factors Produced in Response to Exercise

Biomedicines, Journal Year: 2024, Volume and Issue: 12(9), P. 1975 - 1975

Published: Sept. 1, 2024

Regular exercise and physical activity are now considered lifestyle factors with positive effects on human health. Physical reduces disease burden, protects against the onset of pathologies, improves clinical course disease. Unlike pharmacological therapies, mediated by not limited to a specific target organ but act in multiple biological systems simultaneously. Despite substantial health benefits training, precise molecular signaling processes that lead structural functional tissue adaptation remain largely unknown. Only recently, several bioactive molecules have been discovered produced following exercise. These collectively called “exerkines”. Exerkines released from various tissues response exercise, play crucial role mediating beneficial body. Major discoveries involving exerkines highlight their diverse functions implications, particularly metabolic regulation, neuroprotection, muscle adaptation. molecules, including peptides, nucleic acids, lipids, microRNAs, through paracrine, endocrine, autocrine pathways exert organs tissues. represent complex network mediate Their roles importance maintaining preventing

Language: Английский

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Myokines and Microbiota: New Perspectives in the Endocrine Muscle–Gut Axis

Nutrients, Journal Year: 2024, Volume and Issue: 16(23), P. 4032 - 4032

Published: Nov. 25, 2024

This review explores the dual role of skeletal muscle as both a mechanical and endocrine organ, highlighting its contributions to overall health adaptability various inputs such nutrition, hormones, exercise, injuries. In addition in metabolism energy conversion, secretes signalling molecules called myokines (at rest) exerkines (during/after physical exercise), which communicate with other organs like brain, cardiovascular system, immune system. Key interleukins, irisin, myostatin are discussed for their roles mediating inter-organ communication. work also focuses on muscle-gut axis, emphasising bidirectional interaction between gut microbiota, complex ecosystem influencing defence, digestion, metabolism. Muscle activity, particularly alters microbial composition, promoting beneficial species, while gut-derived metabolites short-chain fatty acids (SCFAs) impact metabolism, mitochondrial function, insulin sensitivity. Dysbiosis, or an imbalanced can lead atrophy, inflammation, metabolic dysfunction. evidence highlights emerging research into potential therapeutic targets managing conditions decline, ageing, diseases through interactions.

Language: Английский

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