Potential role of tanycyte-derived neurogenesis in Alzheimer’s disease DOI Creative Commons
Guibo Qi, Han Tang, Jianian Hu

и другие.

Neural Regeneration Research, Год журнала: 2024, Номер 20(6), С. 1599 - 1612

Опубликована: Июнь 26, 2024

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role generation of new neurons that contribute to neural circuits responsible for regulating systemic energy balance. The precise coordination gene networks controlling neurogenesis naive and mature tanycytes is essential maintaining homeostasis adulthood. However, our understanding molecular mechanisms signaling pathways govern proliferation differentiation into remains limited. This article aims review recent advancements research functions tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed specifically originating from hypothalamus has compensatory neuronal loss helps maintain during metabolic diseases. Intriguingly, disorders are considered early biomarkers Alzheimer's disease. Furthermore, neurogenic potential state newborn derived heavily depend on maintenance mild microenvironments, which may be disrupted disease due impaired blood-brain barrier function. specific alterations regulatory governing remain unclear. Accumulating evidence suggests might disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses challenge because lack long-term tracing nucleus-specific analyses patients with Further underlying holds promise identifying small molecules capable restoring tanycyte neurodegenerative line investigation could provide valuable insights therapeutic strategies related conditions.

Язык: Английский

Game changer: Navigating between challenges and hopes in geropharmacology DOI
Qian Chen,

Robert A. Hartman,

Lidia Dankiv

и другие.

Advances in pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Metformin: Beyond Diabetes Management to Neuroprotection and Cognitive Enhancement DOI
Priyanka Gupta, Sirshak Dutta, Rajiv Jash

и другие.

Current Pharmacology Reports, Год журнала: 2025, Номер 11(1)

Опубликована: Фев. 22, 2025

Язык: Английский

Процитировано

0
Premutation Females with preFXTAS DOI Open Access

Valentina Liani,

Carme Torrents,

Elisa Rolleri

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2825 - 2825

Опубликована: Март 20, 2025

Fragile-X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder associated with the FMR1 gene premutation, characterized by presence of 55 to 200 CGG triplet repeat expansions. Although initial symptoms FXTAS typically manifest in males around age 60 motor and cognitive deficits, presentation progression females differ. Women, fact, exhibit higher prevalence neuropsychiatric symptoms, an earlier onset compared observed men. The following article reports on ten cases women diagnosis originating from two medical centers. All study exhibited subtle neurological signs as common features. Symptoms male population, such tremors cerebellar ataxia, were either absent or significantly reduced female cohort. Conversely, there was among women. Neurocognitive impairment only minimally evident, mild executive dysfunction memory complaints noted subset cases. For this reason, we propose terminology preFXTAS prodromic define clinical early manifestations that do not entirely fulfill established diagnostic criteria but MRI evidence white matter alterations suggesting initiation disease process. underscores importance establishing new for and, at same time, developing biomarkers interview checklists/assessment scales dedicated females.

Язык: Английский

Процитировано

0
Metformin Improves Spatial Memory and Reduces Seizure Severity in a Rat Model of Epilepsy and Alzheimer’s Disease comorbidity via PI3K/Akt Signaling Pathway DOI

Suélen Santos Alves,

Letícia Rossi,

José Antônio Cortes de Oliveira

и другие.

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Язык: Английский

Процитировано

0
Transcriptome Sequencing Analysis of the Effects of Metformin on the Regeneration of Planarian Dugesia japonica DOI Open Access
Zelong Zhao, Dandan Yin, Kexin Yang

и другие.

Genes, Год журнала: 2025, Номер 16(4), С. 365 - 365

Опубликована: Март 22, 2025

Background: Metformin is a widely used oral hypoglycemic agent for treating type 2 diabetes. Planarians, with their remarkable regenerative abilities, are frequently employed as model organisms in stem cell and regeneration studies. This study aimed to investigate the effects of metformin on planarian regeneration, focusing eyespots after amputation. Methods: Regenerating planarians amputated were exposed various concentrations metformin. The time was measured assess Subsequently, 1 mmol/L treatment 24 h applied planarians, followed by transcriptome analysis identify differentially expressed genes (DEGs). gene expression validated through qPCR. full-length casein kinase 1α (DjCK1α) cloned using RACE technology. DjCK1α interference performed examine its role regeneration. Results: Low significantly reduced planarians. Transcriptome identified 113 DEGs, including 61 upregulated 52 downregulated genes. GO KEGG enrichment analyses conducted. Notably, DjCK1α, key involved selected further validation. qPCR confirmed that upregulated. prolonged cultured water, while did not promote eyespot DjCK1α-interfered Conclusions: results suggest accelerates potentially regulation DjCK1α. provides first transcriptome-based drug highlighting process.

Язык: Английский

Процитировано

0
Overview of Metformin and Neurodegeneration: A Comprehensive Review DOI Creative Commons
Weronika Kruczkowska, Julia Gałęziewska, Paulina Buczek

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(4), С. 486 - 486

Опубликована: Март 28, 2025

This comprehensive review examines the therapeutic potential of metformin, a well-established diabetes medication, in treating neurodegenerative disorders. Originally used as first-line treatment for type 2 diabetes, recent studies have begun investigating metformin’s effects beyond metabolic disorders, particularly its neuroprotective capabilities against conditions like Parkinson’s disease, Alzheimer’s Huntington’s and multiple sclerosis. Key findings demonstrate that operate through pathways: AMPK activation enhancing cellular energy metabolism autophagy; upregulation antioxidant defenses; suppression inflammation; inhibition protein aggregation; improvement mitochondrial function. These mechanisms collectively address common pathological features neurodegeneration neuroinflammation, including oxidative stress, accumulation, dysfunction. Clinical preclinical evidence supporting association with improved cognitive performance, reduced risk dementia, modulation hallmarks diseases is critically evaluated. While metformin shows promise agent, this emphasizes need further investigation to fully understand optimal applications diseases.

Язык: Английский

Процитировано

0
Effects of Prebiotic Phytocompound Administration in Gestational Diabetic Dams and Its Influence on Offspring Cognitive Outcomes DOI Open Access

Gayathri Jagadeesan,

Tushar Kanti Das,

J. Mulero Mendoza

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3140 - 3140

Опубликована: Март 28, 2025

Gestational diabetes mellitus (GD)-induced gut dysbiosis in pregnant mothers may increase the risk of cognitive impairment and neurological disorders both mother offspring as they age. Restoring balance could improve outcomes for both. Despite advancements GD treatment, side effects have increased, long-term neurocognitive impacts on born to remain underexplored. This study uses a mouse model, inducing pancreatic dysfunction 3-month-old C57BL/6J mice with Streptozotocin. The efficacy mechanism prebiotic phytocompound green leaf extract (Allmania nodiflora) were assessed, metformin standard. dams exhibited weight glucose reduction, IL-6 elevation, GLUT3 astroglia changes cerebral cortex, barrier impairment, heightened anxiety compared controls. Bacterial 16s rRNA sequencing revealed dysbiosis, reduced Erysipelotrichales Metformin lowered blood levels but failed rescue functional behavioral phenotypes offspring. Phytocompound treatment improved glucose, inflammation, integrity, reversed enhanced brain health. It rescued deficits offspring, suggesting be more effective therapeutic agent humans.

Язык: Английский

Процитировано

0
Metformin attenuates central sensitization by regulating neuroinflammation through the TREM2-SYK signaling pathway in a mouse model of chronic migraine DOI Creative Commons
Zhenzhen Fan, Dandan Su,

Zi Chao Li

и другие.

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Дек. 3, 2024

Chronic migraine (CM) is a serious neurological disorder. Central sensitization one of the important pathophysiological mechanisms underlying CM, and microglia-induced neuroinflammation conduces to central sensitization. Triggering receptor expressed on myeloid cells 2 (TREM2) presented solely in microglia residing within nervous system plays key role neuroinflammation. Metformin has been shown regulate inflammatory responses exert analgesic effects, but its relationship with CM remains unclear. In study, we investigated whether metformin modulates TREM2 improve clarified potential molecular mechanisms. A mouse model was induced by administration nitroglycerin (NTG). Behavioral evaluations were conducted using von Frey filaments hot plate experiments. Western blot immunofluorescence techniques employed investigate SYK inhibitor R406 administered mice assess their regulatory effects To explore TREM2-SYK regulating metformin, lentivirus encoding injected into trigeminal nucleus caudalis (TNC). vitro experiments evaluate regulation involving interventions LPS, R406, siTREM2, plasmids. pretreatment can effectively hyperalgesia mice. Both significantly inhibit c-fos CGRP expression mice, suppressing activation NLRP3 inflammasome NTG. With NTG, gradually increased TNC microglia. Additionally, observed that inhibits Lv-TREM2 attenuated metformin-mediated anti-inflammatory responses. experiments, knockdown inhibited LPS-induced pathway alleviated After sole overexpression TREM2, signaling activated, resulting an pro-inflammatory cytokines; nevertheless, this consequence be reversed R406. The attenuates inhibition activity mediated effect Our findings suggest through pathway.

Язык: Английский

Процитировано

3
Intravitreal Metformin Protects Against Choroidal Neovascularization and Light-Induced Retinal Degeneration DOI Open Access
Jason Xiao, Wendy Luo, Amir Mani

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(21), С. 11357 - 11357

Опубликована: Окт. 22, 2024

Neovascular age-related macular degeneration (nAMD), a leading cause of blindness in older adults, presents challenging pathophysiology involving choroidal neovascularization (CNV) and retinal degeneration. Current treatments relying on intravitreal (IVT) administration anti-angiogenic agents are costly moderate effectiveness. Metformin, the common anti-diabetic drug, has been associated with decreased odds developing AMD. Studies have shown that metformin can mitigate cellular aging, neoangiogenesis, inflammation across multiple diseases. This preclinical study assessed metformin's impact vessel growth using explants before exploring IVT effects laser-induced CNV light-induced C57BL/6J BALB/cJ mice, respectively. Metformin reduced new dose-dependent relationship. Following laser induction, suppressed peripheral infiltration IBA1

Язык: Английский

Процитировано

2
The Role and Mechanism of Metformin in the Treatment of Nervous System Diseases DOI Creative Commons
Hui Li, Ruhui Liu, Junyan Liu

и другие.

Biomolecules, Год журнала: 2024, Номер 14(12), С. 1579 - 1579

Опубликована: Дек. 10, 2024

Nervous system diseases represent a significant global burden, affecting approximately 16% of the world’s population and leading to disability mortality. These conditions, encompassing both central nervous (CNS) peripheral (PNS) disorders, have substantial social economic impacts. Metformin, guanidine derivative derived from plant source, exhibits therapeutic properties in various health conditions such as cancer, aging, immune-related polycystic ovary syndrome, cardiovascular ailments, more. Recent studies highlight metformin’s ability cross blood–brain barrier, stimulate neurogenesis, provide beneficial effects specific neurological disorders through diverse mechanisms. This review discusses advancements research on role mechanisms treating within systems, aiming facilitate further investigation, utilization, clinical application metformin neurology.

Язык: Английский

Процитировано

2