Mitochondrial and metabolic dysfunction in ageing and age-related diseases

Nature Reviews Endocrinology, Год журнала: 2022, Номер 18(4), С. 243 - 258

Опубликована: Фев. 10, 2022

Язык: Английский

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Microglia in the Neuroinflammatory Pathogenesis of Alzheimer’s Disease and Related Therapeutic Targets

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Апрель 26, 2022

Alzheimer's disease (AD) is the most prevalent neurodegenerative worldwide, characterized by progressive neuron degeneration or loss due to excessive accumulation of β-amyloid (Aβ) peptides, formation neurofibrillary tangles (NFTs), and hyperphosphorylated tau. The treatment AD has been only partially successful as majority pharmacotherapies on market may alleviate some symptoms. In occurrence AD, increasing attention paid neurodegeneration, while resident glial cells, like microglia are also observed. Microglia, a kind crucial cells associated with innate immune response, functions double-edge sword role in CNS. They exert beneficial detrimental influence adjacent neurons through secretion both pro-inflammatory cytokines well neurotrophic factors. addition, their endocytosis debris toxic protein Aβ tau ensures homeostasis neuronal microenvironment. this review, we will systematically summarize recent research regarding roles pathology latest microglia-associated therapeutic targets mainly including genes, anti-inflammatory genes phagocytosis at length, which contradictory controversial warrant further be investigated.

Язык: Английский

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Metformin and Insulin Resistance: A Review of the Underlying Mechanisms behind Changes in GLUT4-Mediated Glucose Transport

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1264 - 1264

Опубликована: Янв. 23, 2022

Metformin is the most commonly used treatment to increase insulin sensitivity in insulin-resistant (IR) conditions such as diabetes, prediabetes, polycystic ovary syndrome, and obesity. There a well-documented correlation between glucose transporter 4 (GLUT4) expression level of IR. Therefore, observed peripheral utilization after metformin likely comes from induction GLUT4 its increased translocation plasma membrane. However, mechanisms behind this effect critical targets are still largely undefined. The present review explores evidence for crucial role changes activation signaling pathway mediators, AMPK, several posttranscriptional modifications based on previously published preclinical clinical models metformin's mode action animal human studies. Our aim provide comprehensive studies field order shed some light complex interactions action, expression, translocation, sensitivity.

Язык: Английский

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Drug repurposing for cancer therapy

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Апрель 18, 2024

Abstract Cancer, a complex and multifactorial disease, presents significant challenge to global health. Despite advances in surgical, radiotherapeutic immunological approaches, which have improved cancer treatment outcomes, drug therapy continues serve as key therapeutic strategy. However, the clinical efficacy of is often constrained by resistance severe toxic side effects, thus there remains critical need develop novel therapeutics. One promising strategy that has received widespread attention recent years repurposing: identification new applications for existing, clinically approved drugs. Drug repurposing possesses several inherent advantages context since repurposed drugs are typically cost-effective, proven be safe, can significantly expedite development process due their already established safety profiles. In light this, present review offers comprehensive overview various methods employed repurposing, specifically focusing on treat cancer. We describe antitumor properties candidate drugs, discuss detail how they target both hallmarks tumor cells surrounding microenvironment. addition, we examine innovative integrating with nanotechnology enhance topical delivery. also emphasize role play when used part combination regimen. To conclude, outline challenges associated consider future prospects these transitioning into application.

Язык: Английский

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Targeting aging mechanisms: pharmacological perspectives

Trends in Endocrinology and Metabolism, Год журнала: 2022, Номер 33(4), С. 266 - 280

Опубликована: Фев. 17, 2022

Язык: Английский

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Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes

Drug Design Development and Therapy, Год журнала: 2023, Номер Volume 17, С. 1907 - 1932

Опубликована: Июнь 1, 2023

Metformin has been designated as one of the most crucial first-line therapeutic agents in management type 2 diabetes mellitus. Primarily being an antihyperglycemic agent, metformin also a plethora pleiotropic effects on various systems and processes. It acts majorly by activating AMPK (Adenosine Monophosphate-Activated Protein Kinase) cells reducing glucose output from liver. decreases advanced glycation end products reactive oxygen species production endothelium apart regulating lipid metabolism cardiomyocytes, hence minimizing cardiovascular risks. Its anticancer, antiproliferative apoptosis-inducing malignant might prove instrumental malignancy organs like breast, kidney, brain, ovary, lung, endometrium. Preclinical studies have shown some evidence metformin's neuroprotective role Parkinson's disease, Alzheimer's multiple sclerosis Huntington's disease. exerts its through varied pathways intracellular signalling exact mechanism majority them remains yet to be clearly defined. This article extensively reviewed benefits details for molecule boon conditions diabetes, prediabetes, obesity, polycystic ovarian metabolic derangement HIV, cancers aging.

Язык: Английский

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Stress-Induced Diabetes: A Review

Cureus, Год журнала: 2022, Номер unknown

Опубликована: Сен. 13, 2022

It has long been established that stress a significant impact on metabolic function. Type 2 diabetes may be initiated by psychological and physical stress. The central peripheral nervous systems are both involved in the neuroendocrine framework underlies underlying processes. release of catecholamines rise serum glucocorticoid concentrations caused enhance requirement for insulin resistance. Experiencing persistent hyperglycemia people with influenced Blood sugar levels due to hormones being released response Although this adaptive significance healthy patient, run, it can cause resistance lead diabetes. Additionally, abnormalities regulation these hormones.

Язык: Английский

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Management of diabesity: Current concepts

World Journal of Diabetes, Год журнала: 2023, Номер 14(4), С. 396 - 411

Опубликована: Апрель 11, 2023

The global prevalence of obesity is increasing rapidly with an exponential rise in incidence type 2 diabetes mellitus recent years. 'Diabesity', the term coined to show strong interlink between and diabetes, direct cons-equence pandemic, poses significant challenges management disease. Without addressing clinical mechanistic complications such as metabolic-associated fatty liver disease obstructive sleep apnoea, a rational algorithm for diabesity cannot be developed. Several classes anti-diabetic medications including insulins, sulphonylureas, thiazolidinediones meglitinides are associated risk weight gain may potentially worsen diabesity. Therefore, appropriate selection antidiabetic drug regimen crucial medical role non-pharmacological measures dietary adjustments, exercise interventions bariatric procedures should also emphasised. Unfortunately, importance optimal often overlooked by professionals when achieving adequate glycemic control which results inappropriate its complications. This review provides narrative update on evidence behind

Язык: Английский

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Exercise mimetics: a novel strategy to combat neuroinflammation and Alzheimer’s disease

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

Опубликована: Фев. 2, 2024

Abstract Neuroinflammation is a pathological hallmark of Alzheimer’s disease (AD), characterized by the stimulation resident immune cells brain and penetration peripheral cells. These inflammatory processes facilitate deposition amyloid-beta (Aβ) plaques abnormal hyperphosphorylation tau protein. Managing neuroinflammation to restore homeostasis decrease neuronal damage therapeutic approach for AD. One way achieve this through exercise, which can improve function protect against neuroinflammation, oxidative stress, synaptic dysfunction in AD models. The neuroprotective impact exercise regulated various molecular factors that be activated same as administration their mimetics. Recent evidence has proven some mimetics effective alleviating AD, and, additionally, they are helpful alternative option patients who unable perform regular physical manage neurodegenerative disorders. This review focuses on current state knowledge mimetics, including efficacy, regulatory mechanisms, progress, challenges, limitations, future guidance application therapy.

Язык: Английский

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Metformin as anticancer agent and adjuvant in cancer combination therapy: Current progress and future prospect

Translational Oncology, Год журнала: 2024, Номер 44, С. 101945 - 101945

Опубликована: Март 30, 2024

Metformin, as the preferred antihyperglycemic drug for type 2 diabetes, has been found to have a significant effect in inhibiting tumor growth recent years. However, metformin alone cancer treatment disadvantages of high dose concentrations and few targeted types. Increasing studies confirmed that can be used combination with conventional anticancer therapy obtain more promising clinical benefits, which is expected rapidly transformed applied clinic. Some strategies including combined chemotherapy, radiotherapy, immunotherapy proven antitumor effects longer survival time than monotherapy. In this review, we summarize synergistic mechanisms other current therapies. addition, update research progress latest prospect metformin-combined application treatment. This work could provide evidence future direction antitumor.

Язык: Английский

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