Unveiling FOXO3's metabolic contribution to menopause and Alzheimer's disease

Experimental Gerontology, Journal Year: 2025, Volume and Issue: 200, P. 112679 - 112679

Published: Jan. 9, 2025

The increasing prevalence of Alzheimer's disease (AD) calls for a comprehensive exploration its complex etiology, with focus on sex-specific vulnerability, particularly the heightened susceptibility observed in postmenopausal women. Neurometabolic alterations during endocrine transition emerge as early indicators AD pathology, including reduced glucose metabolism and increased amyloid-beta (Aβ) deposition. fluctuating environment, marked by declining estradiol levels estrogen receptor beta (ERβ) activity, further exacerbates this process. In context, here we explore potential forkhead box O3 (FOXO3) critical mediator linking metabolic disturbances to hormonal decline. We propose that FOXO3 plays key role intersection menopause AD, given dysregulation both patients women, modulating cellular through interactions AMPK/AKT/PI3K pathways. This relationship highlights between changes susceptibility. review aims open discussion FOXO3's contribution seen impact progression AD. Understanding functional menopause-associated could lead targeted therapeutic strategies, offering novel insights managing condition.

Language: Английский

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How Hormonal Balance Changes Lives in Women with Psoriasis

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 582 - 582

Published: Jan. 17, 2025

Psoriasis is a chronic, immune-mediated skin disease significantly impacting women, with severity often modulated by hormonal fluctuations. This review examines the influence of changes on course psoriasis in focusing key life stages—including menstrual cycle, pregnancy, postpartum, and menopause—and their impact progression symptomatology. Estrogen, principal female sex hormone, plays critical role immune modulation. Variations estrogen levels, which occur naturally throughout woman’s life, are associated fluctuations severity. Low as seen during menstruation or menopause, linked to symptom exacerbation, while elevated levels pregnancy may reduce symptoms some women. However, responses variable, others experiencing no change worsening pregnancy. Postpartum, rapid decline triggers severe flare-ups, marked sustained reduction, frequently correlates increased flare frequency. The also addresses profound women’s quality including physical discomfort, psychological distress, social stigma. Additionally, fertility concerns discussed, treatments increase risk adverse outcomes. Consideration given therapies, lifestyle modifications, effects psoriasis, underscoring need for personalized treatment approaches that account influences. Understanding these dynamics essential developing targeted, effective management strategies enhance women affected psoriasis.

Language: Английский

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LncRNA PVT1 links estrogen receptor alpha and the polycomb repressive complex 2 in suppression of pro-apoptotic genes in hormone-responsive breast cancer

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 8, 2025

RNA-based therapeutics highlighted novel approaches to target either coding or noncoding molecules for multiple diseases treatment. In breast cancer (BC), a multitude of deregulated long RNAs (lncRNAs) have been identified as potential therapeutic targets also in the context antiestrogen resistance, and RNA binding activity estrogen receptor α (ERα) points additional candidates interfere with estrogenic signaling. A set lncRNAs was selected among ERα-associated BC cell nuclei due their roles processes such transcriptional regulation epigenetic chromatin modifications. Native immunoprecipitation nuclear ERα-interacting coupled NGS (RIP-Seq) performed MCF-7 cells, leading identification essential interacting multi-molecular regulatory complexes. Among these, PVT1, FGD5-AS1 EPB41L4A-AS1 were further investigation. Functional assays transcriptome analysis following lncRNA knock-down indicated PVT1 master modulator some most relevant hallmarks, proliferation, apoptosis, migration response hypoxia. addition, targeted experiments key factor composition PRC2-ERα network involved downregulation tumor suppressor genes, including BTG2.

Language: Английский

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Ovarian Aging: The Silent Catalyst of Age-Related Disorders in Female Body

Aging and Disease, Journal Year: 2025, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2025

Age-related diseases have emerged as a global concern the population ages. Consequently, understanding underlying causes of aging and exploring potential anti-aging interventions is imperative. In females, ovaries serve principal organs responsible for ovulation production female hormones. The are related to infertility, menopause, associated menopausal syndromes, with menopause representing culmination ovarian aging. Current evidence indicates that may contribute dysfunction across multiple organ systems, including, but not limited to, cognitive impairment, osteoporosis, cardiovascular disease. Nevertheless, due widespread distribution sex hormone receptors throughout body, affects only these specific also influences broader spectrum age-related in women. Despite this, impact on overall has been largely neglected. This review provides thorough summary diseases, encompassing nervous, circulatory, locomotor, urinary, digestive, respiratory, endocrine systems. Additionally, we outlined prospective therapeutic approaches addressing both aim mitigating their impacts preserving women's fertility, physical health, psychological well-being.

Language: Английский

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The intersection of aging and estrogen in osteoarthritis

npj Women s Health, Journal Year: 2025, Volume and Issue: 3(1)

Published: Feb. 25, 2025

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage degradation, inflammation, and pain. While multiple factors contribute to OA development, age sex are primary risk factors, particularly affecting postmenopausal women. The dramatic increase in after menopause suggests estrogen deficiency accelerates progression. This review explores the molecular mechanisms connecting aging focusing on key genes pathways identified through RNA sequencing.

Language: Английский

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Phytochemicals Modulate Biosynthesis and Function of Serotonin, Dopamine, and Norepinephrine for Treatment of Monoamine Neurotransmission-Related Psychiatric Diseases

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2916 - 2916

Published: March 23, 2025

Serotonin (5-HT), dopamine (DA), and norepinephrine (NE) are key monoamine neurotransmitters regulating behaviors, mood, cognition. 5-HT affects early brain development, its dysfunction induces vulnerability to stress, raising the risk of depression, anxiety, autism in adulthood. These synthesized from tryptophan tyrosine via hydroxylation decarboxylation, metabolized by oxidase (MAO). This review aims summarize current findings on role dietary phytochemicals modulating neurotransmitter biosynthesis, metabolism, function, with an emphasis their potential therapeutic applications neuropsychiatric disorders. Phytochemicals exert antioxidant, neurotrophic, neurohormonal activities, regulate gene expression, induce epigenetic modifications. Phytoestrogens activate estrogen receptors or estrogen-responsive elements promoter target genes, enhance transcription hydroxylase hydroxylase, while inhibiting that MAO. compounds also influence interaction between genetic environmental factors, potentially reversing dysregulated neurotransmission architecture associated conditions. Despite promising preclinical findings, clinical remain challenging. Advances nanotechnology targeted delivery systems offer solutions efficacy. discusses mechanisms, challenges, strategies, underscoring need for further research advance phytochemical-based interventions diseases.

Language: Английский

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FXR and NASH: an avenue for tissue-specific regulation

Hepatology Communications, Journal Year: 2023, Volume and Issue: 7(5)

Published: April 14, 2023

NASH is within the spectrum of NAFLD, a liver condition encompassing steatosis, inflammation, hepatocyte injury, and fibrosis. The prevalence NASH-induced cirrhosis rapidly rising has become leading indicator for transplantation in US. There no Food Drug Administration (FDA)-approved pharmacological intervention NASH. farnesoid X receptor (FXR) essential regulating bile acid homeostasis, dysregulation acids been implicated pathogenesis As result, modulators FXR that show desirable effects mitigating key characteristics have developed as promising therapeutic approaches. However, global activation causes adverse such cholesterol homeostasis imbalance pruritus. development targeted modulation necessary ideal therapeutics, but information regarding tissue-specific cell-specific functionality limited. In this review, we highlight regulation development, examine current literature on nuclear receptors, speculate how will be beneficial treatment

Language: Английский

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Phytoestrogens: Chemistry, potential health benefits, and their medicinal importance

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(6), P. 3060 - 3079

Published: April 11, 2024

Abstract Phytoestrogens, also known as xenoestrogens, are secondary metabolites derived from plants that have similar structures and biological effects human estrogens. These compounds do not directly affect functions but can act agonists or antagonists depending on the level of endogenous estrogen in body. Phytoestrogens may an epigenetic mechanism action independent receptors. found more than 300 plant species synthesized through phenylpropanoid pathway, with specific enzymes leading to various chemical structures. primarily phenolic compounds, include isoflavonoids, flavonoids, stilbenes, lignans. Extensive research animals humans has demonstrated protective phytoestrogens estrogen‐dependent diseases. Clinical trials shown their potential benefits conditions such osteoporosis, Parkinson's disease, certain types cancer. This review provides a concise overview phytoestrogen classification, diversity, biosynthesis discusses therapeutic phytoestrogens, well preclinical clinical development.

Language: Английский

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Discovery of Novel ERα and Aromatase Dual-Targeting PROTAC Degraders to Overcome Endocrine-Resistant Breast Cancer

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(11), P. 8913 - 8931

Published: May 29, 2024

Estrogen receptor α (ERα) plays a pivotal role in the proliferation, differentiation, and migration of breast cancer (BC) cells, aromatase (ARO) is crucial enzyme estrogen synthesis. Hence, it necessary to inhibit production or activity ERα for treatment receptor-positive (ER

Language: Английский

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Disease clusters subsequent to anxiety and stress-related disorders and their genetic determinants

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 8, 2024

Abstract Anxiety/stress-related disorders have been associated with multiple diseases, whereas a comprehensive assessment of the structure and interplay subsequent diseases their genetic underpinnings is lacking. Here, we first identify 136, out 454 tested, medical conditions incident anxiety/stress-related attended in specialized care using population-based cohort from nationwide Swedish Patient Register, comprising 70,026 patients 1:10 birth year- sex-matched unaffected individuals. By combining findings comorbidity network disease trajectory analyses, five robust clusters to be prior diagnosis disorders, featured by predominance psychiatric eye ear cardiovascular skin genitourinary diseases. These are largely validated UK Biobank. GWAS analyses based on Biobank 3, 33, 40, 4, 16 significantly independent single nucleotide polymorphisms for link clusters, respectively, which mapped several distinct risk genes biological pathways. motivate further mechanistic explorations aid early cluster-based prevention among newly diagnosed care.

Language: Английский

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