Insights and implications of sexual dimorphism in osteoporosis

Bone Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Feb. 18, 2024

Osteoporosis, a metabolic bone disease characterized by low mineral density and deterioration of microarchitecture, has led to high risk fatal osteoporotic fractures worldwide. Accumulating evidence revealed that sexual dimorphism is notable feature osteoporosis, with sex-specific differences in epidemiology pathogenesis. Specifically, females are more susceptible than males while prone disability or death from the disease. To date, sex chromosome abnormalities steroid hormones have been proven contribute greatly osteoporosis regulating functions cells. Understanding its related complications essential for improving treatment strategies tailored women men. This literature review focuses on mechanisms underlying mainly population aging patients, chronic glucocorticoid administration, diabetes. Moreover, we highlight implications developing therapeutics preventive screening approaches Additionally, challenges translating bench research bedside treatments future directions overcome these obstacles will be discussed.

Language: Английский

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AdipoRon’s Impact on Alzheimer’s Disease—A Systematic Review and Meta-Analysis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 484 - 484

Published: Jan. 8, 2025

Alzheimer's disease (AD) remains a leading cause of cognitive decline and mortality worldwide, characterized by neurodegeneration, synaptic deficiencies, neuroinflammation. Despite advancements in early detection, diagnosis, treatment, AD presents substantial challenges due to its complex pathology, heterogeneity, the limited efficacy current therapies. Consequently, there is pressing need for novel therapeutic agents target multifaceted aspects enhance treatments, minimize adverse effects. AdipoRon, an adiponectin receptor agonist, has garnered interest potential neuroprotective effects, including reducing neuroinflammation, improving mitochondrial function, mitigating tau hyperphosphorylation. This review aimed evaluate effects AdipoRon-based replacement therapy against AD, using comprehensive approach grounded PICO framework-Population, Intervention, Comparison, Outcomes. A total six studies were reviewed, vitro vivo investigations examining AdipoRon's impact on various models. These involved different cell lines transgenic mouse models, assessing outcomes such as phosphorylation, relevant molecular pathways. By synthesizing data from these studies, our thoroughly explains mechanisms action, agent AD. analysis aims highlight state knowledge, identify gaps research, suggest directions future clinical applications.

Language: Английский

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Estrogen-immuno-neuromodulation disorders in menopausal depression

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: June 19, 2024

Abstract A significant decrease in estrogen levels puts menopausal women at high risk for major depression, which remains difficult to cure despite its relatively clear etiology. With the discovery of abnormally elevated inflammation depressed women, immune imbalance has become a novel focus study depression. In this paper, we examined characteristics and possible mechanisms caused by decreased during menopause found that deficiency disrupted homeostasis, especially inflammatory cytokines through ERα/ERβ/GPER-associated NLRP3/NF-κB signaling pathways. We also analyzed destruction blood-brain barrier, dysfunction neurotransmitters, blockade BDNF synthesis, attenuation neuroplasticity cytokine activity, investigated estrogen-immuno-neuromodulation disorders Current research suggests drugs targeting molecules are promising restoring homeostasis system may play positive role intervention treatment

Language: Английский

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Dementia and Alzheimer's Disease Associated With Aromatase Inhibitors: A Disproportionality Analysis of the WHO Pharmacovigilance Database (VigiBase)

Pharmacology Research & Perspectives, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 1, 2025

Aromatase inhibitors are used for patients with hormone-receptor positive breast cancer. Alzheimer's disease is the most prevalent cause of dementia. Several studies have suggested an association between use aromatase and development disease. The objective this study was to identify potential pharmacovigilance signals associated dementia third-generation in menopausal postmenopausal women. VigiBase, global database individual case safety reports World Health Organization, investigate possible association. A disproportionality analysis performed women aged 45 years older. reporting odds ratio (ROR) its 95% CI exemestane, 2.08 (1.35-3.19); anastrozole, 1.59 (1.09-2.32); letrozole, 1.43 (1.05-1.95) 0.94 (0.30-2.92); anastrozole: 2.63 (1.55-4.45); 1.33 (0.76-2.35). For senile dementia, only letrozole has cases, ROR 6.77 (2.51-18.31). Signals disproportionate been observed occurrence type, inhibitors, which line estrogen functions activity, as well findings from preclinical studies. Additional research required elucidate intricate matter.

Language: Английский

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Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System

Biomolecules, Journal Year: 2023, Volume and Issue: 13(5), P. 816 - 816

Published: May 11, 2023

It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning knowledge that disease intimately tied to neurodegenerative disorders, affecting both central and peripheral nervous systems well leading dementia, seventh cause of death. New innovative therapeutic strategies address metabolism, apoptosis, autophagy, pyroptosis, mechanistic target rapamycin (mTOR), AMP activated protein kinase (AMPK), growth factor signaling with erythropoietin (EPO), risk factors apolipoprotein E (APOE-ε4) gene coronavirus 2019 (COVID-19) can offer valuable insights for clinical care treatment disorders impacted by disease. Critical insight into modulation these complex pathways are required since mTOR pathways, AMPK activation, improve memory retention in Alzheimer's (AD) DM, promote healthy aging, facilitate clearance β-amyloid (Aß) tau brain, control inflammation, but also may lead cognitive loss long-COVID syndrome through mechanisms include oxidative stress, mitochondrial cytokine release, APOE-ε4 if autophagy other programmed cell death left unchecked.

Language: Английский

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The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 8, 2023

Life expectancy is increasing throughout the world and coincides with a rise in non-communicable diseases (NCDs), especially for metabolic disease that includes diabetes mellitus (DM) neurodegenerative disorders. The debilitating effects of disorders influence entire body significantly affect nervous system impacting greater than one billion people disability peripheral as well cognitive loss, now seventh leading cause death worldwide. Metabolic disorders, such DM, neurologic remain significant challenge treatment care individuals since present therapies may limit symptoms but do not halt overall progression. These clinical challenges to address interplay between warrant innovative strategies can focus upon underlying mechanisms aging-related oxidative stress, cell senescence, death. Programmed pathways involve autophagy, apoptosis, ferroptosis, pyroptosis play critical role oversee processes include insulin resistance, β-cell function, mitochondrial integrity, reactive oxygen species release, inflammatory activation. silent mating type information regulation 2 homolog 1

Language: Английский

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Molecular Mechanisms of the Anti-Inflammatory Effects of Epigallocatechin 3-Gallate (EGCG) in LPS-Activated BV-2 Microglia Cells

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(4), P. 632 - 632

Published: April 7, 2023

Chronic neuroinflammation is associated with many neurodegenerative diseases, such as Alzheimer's. Microglia are the brain's primary immune cells, and when activated, they release various proinflammatory cytokines. Several natural compounds anti-inflammatory antioxidant properties, epigallocatechin 3-gallate (EGCG), may provide a promising strategy for inflammation-related diseases involving activated microglia cells. The objective of current study was to examine molecular targets underlying effects EGCG in BV-2 cells were grown, stimulated, treated EGCG. Cytotoxicity nitric oxide (NO) production evaluated. Immunoassay, PCR array, WES™ Technology utilized evaluate inflammatory, neuroprotective modulators well signaling pathways involved mechanistic action neuroinflammation. Our findings showed that significantly inhibited mediator NO LPS-stimulated In addition, ELISA analysis revealed decreases cytokine IL-6 while it increases TNF-α. array downregulated MIF, CCL-2, CSF2. It also upregulated IL-3, IL-11, TNFS10. Furthermore, inflammatory mRNA expression mTOR, NF-κB2, STAT1, Akt3, CCL5, SMAD3 upregulating Ins2, Pld2, A20/TNFAIP3, GAB1. Additionally, reduced relative protein Akt3. These suggest be used its prevent diseases.

Language: Английский

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The Role of Estrogen Therapy as a Protective Factor for Alzheimer’s Disease and Dementia in Postmenopausal Women: A Comprehensive Review of the Literature

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 6, 2023

The complete cessation of menstruation for 12 months with associated vasomotor symptoms is termed menopause. Apart from playing a role in reproduction, estrogen significantly affects the central nervous system (CNS). Population-based studies highlighted substantial difference prevalence dementia between men and women, Alzheimer-associated being more prevalent indicating that deficiency might be risk factor neurodegenerative diseases. Patients experience progressive decline neurocognitive function, beginning short-term memory loss progresses to long-term inability perform everyday activities, leading ultimately death. There currently no cure dementia, so preventing or slowing disease’s progression paramount. Accordingly, researchers have widely studied as neuroprotective agent. Estrogen prevents by augmenting Hippocampal prefrontal cortex reducing neuroinflammation, degradation receptors, decreasing oxidative damage brain, increasing cholinergic serotonergic function. According window phase hypothesis, estrogen’s effect on pronounced if therapy started early, during first five years Other like Woman’s Health Initiative Memory Study (WHIMS) showed unfavorable effects brain. This review aims establish an understanding available data neurodegeneration, namely, Alzheimer’s disease.

Language: Английский

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Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough

European Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 60(1), P. 3466 - 3490

Published: May 10, 2024

Abstract In females, Alzheimer's disease (AD) incidences increases as compared to males due estrogen deficiency after menopause. Estrogen therapy is the mainstay for menopause and associated complications. Estrogen, a hormone with multifaceted physiological functions, has been implicated in AD pathophysiology. plays crucial role amyloid precursor protein (APP) processing overall neuronal health by regulating various factors such brain‐derived neurotrophic factor (BDNF), intracellular calcium signalling, death domain‐associated (Daxx) translocation, glutamatergic excitotoxicity, Voltage‐Dependent Anion Channel, Insulin‐Like Growth Factor 1 Receptor, estrogen‐metabolising enzymes apolipoprotein E (ApoE) polymorphisms. All these impact physiology of postmenopausal women. replacement therapies play an important treatment strategy prevent However, use may lead increased risks breast cancer, venous thromboembolism cardiovascular disease. Various therapeutic approaches have used mitigate effects on AD. These include therapy, Selective Receptor Modulators (SERMs), Beta (ERβ)‐Selective Agonists, Transdermal Delivery, Localised Combination Therapies, Metabolism Modulation Alternative Estrogenic Compounds like genistein from soy, notable phytoestrogen plant sources. mechanism via which modulate women not explained earlier thoroughly. Present review will enlighten all molecular mechanisms Along‐with this, association between estrogen, ApoE polymorphisms also be discussed

Language: Английский

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The Role of Estrogen across Multiple Disease Mechanisms

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(8), P. 8170 - 8196

Published: July 29, 2024

Estrogen is a significant hormone that involved in multitude of physiological and pathological processes. In addition to its pivotal role the reproductive system, estrogen also implicated pathogenesis diseases. Nevertheless, previous research on diseases, including Alzheimer’s disease, depression, cardiovascular diabetes, osteoporosis, gastrointestinal estrogen-dependent cancers, has concentrated single disease area, resulting lack comprehensive understanding cross-disease mechanisms. This brought some challenges current treatment methods for these because as potential therapeutic tool not yet fully developed potential. Therefore, this review aims comprehensively explore mechanism seven types The objective study describe relationship between each estrogen, ways which participates regulating mechanisms, outline efficacy treating diseases clinical practice. By studying variety it hoped more accurate theoretical basis guidance future strategies will be provided, thus promoting effective management

Language: Английский

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