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

Ageing Research Reviews, Год журнала: 2024, Номер 101, С. 102480 - 102480

Опубликована: Сен. 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.

Язык: Английский

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Investigating the Interplay Between the Nrf2/Keap1/HO-1/SIRT-1 Pathway and the p75NTR/PI3K/Akt/MAPK Cascade in Neurological Disorders: Mechanistic Insights and Therapeutic Innovations

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 7, 2025

Язык: Английский

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Navigating the Complexities of Neuronal Signaling and Targets in Neurological Disorders: From Pathology to Therapeutics

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177417 - 177417

Опубликована: Фев. 1, 2025

Язык: Английский

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Molecular mechanisms of GDNF/GFRA1/RET and PI3K/AKT/ERK signaling interplay in neuroprotection: Therapeutic strategies for treating neurological disorders

Neuropeptides, Год журнала: 2025, Номер 111, С. 102516 - 102516

Опубликована: Март 12, 2025

Язык: Английский

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Molecular Links Between Circadian Rhythm Disruption, Melatonin, and Neurodegenerative Diseases: An Updated Review

Molecules, Год журнала: 2025, Номер 30(9), С. 1888 - 1888

Опубликована: Апрель 23, 2025

Circadian rhythms are molecular oscillations governed by transcriptional–translational feedback loops (TTFLs) operating in nearly all cell types and fundamental to physiological homeostasis. Key circadian regulators, such as locomotor output cycles kaput (CLOCK), brain muscle ARNT-like 1 (BMAL1), period (PER), cryptochrome (CRY) gene families, regulate intracellular metabolism, oxidative balance, mitochondrial function, synaptic plasticity. disruption is known a central contributor the pathophysiology of neurodegenerative disorders. Disease-specific disruptions clock expression melatoninergic signaling potential early-stage biomarkers. Melatonin, neurohormone secreted pineal gland, modulates expression, stability, inflammatory responses. It also regulates epigenetic metabolic processes through nuclear receptors regulators involved cellular stress pathways, thereby exerting neuroprotective effects maintaining neuronal integrity. This review provides recent findings from past five years, highlighting how dysregulation mediates key disturbances translational circadian-based therapies diseases.

Язык: Английский

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Exploring the Connection Between BDNF/TrkB and AC/cAMP/PKA/CREB Signaling Pathways: Potential for Neuroprotection and Therapeutic Targets for Neurological Disorders

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Май 9, 2025

Язык: Английский

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