Lipotoxicity-polarised macrophage-derived exosomes regulate mitochondrial fitness through Miro1-mediated mitophagy inhibition and contribute to type 2 diabetes development in mice

Diabetologia, Год журнала: 2023, Номер 66(12), С. 2368 - 2386

Опубликована: Авг. 24, 2023

Язык: Английский

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Recent Development in the Understanding of Molecular and Cellular Mechanisms Underlying the Etiopathogenesis of Alzheimer’s Disease

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(8), С. 7258 - 7258

Опубликована: Апрель 14, 2023

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to dementia and patient death. AD characterized by intracellular neurofibrillary tangles, extracellular amyloid beta (Aβ) plaque deposition, neurodegeneration. Diverse alterations have been associated with progression, including genetic mutations, neuroinflammation, blood-brain barrier (BBB) impairment, mitochondrial dysfunction, oxidative stress, metal ion imbalance.Additionally, recent studies shown an association between altered heme metabolism AD. Unfortunately, decades of research drug development not produced any effective treatments for Therefore, understanding the cellular molecular mechanisms underlying pathology identifying potential therapeutic targets are crucial development. This review discusses most common promising discovery. Furthermore, it highlights role in summarizes mathematical models AD, stochastic model effect Aβ on We also summarize treatment strategies these can offer clinical trials.

Язык: Английский

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Insulin resistance as the molecular link between diabetes and Alzheimer's disease

World Journal of Diabetes, Год журнала: 2024, Номер 15(7), С. 1430 - 1447

Опубликована: Июль 8, 2024

Diabetes mellitus (DM) and Alzheimer's disease (AD) are two major health concerns that have seen a rising prevalence worldwide. Recent studies indicated possible link between DM an increased risk of developing AD. Insulin, while primarily known for its role in regulating blood sugar, also plays vital protecting brain functions. Insulin resistance (IR), especially prevalent type 2 diabetes, is believed to play significant AD's development. When insulin signalling becomes dysfunctional, it can negatively affect various functions, making individuals more susceptible defining features, such as the buildup beta-amyloid plaques tau protein tangles. Emerging research suggests addressing insulin-related issues might help reduce or even reverse changes linked This review aims explore rela-tionship AD, with focus on IR. It explores molecular mechanisms by which IR lead assesses current treatments target Understanding IR's connection AD offers new possibilities highlights importance continued this interdisciplinary field.

Язык: Английский

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Neuronal CD59 isoforms IRIS-1 and IRIS-2 as regulators of neurotransmitter release with implications for Alzheimer’s disease

Alzheimer s Research & Therapy, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 7, 2025

Abstract We have previously demonstrated that the intracellular, non-GPI anchored CD59 isoforms IRIS-1 and IRIS-2 (Isoforms Rescuing Insulin Secretion 1 2) are necessary for insulin secretion from pancreatic β-cells. While investigating their expression across human tissues, we identified mRNA in brain, though protein function remained unclear. This study shows presence of both 2 proteins specifically neurons astrocytes. In neuroblastoma cell line (SH-SY5Y), increases upon differentiation into mature neurons. Silencing SH-SY5Y cells reduces SNARE complex formation, essential synaptic vesicle exocytosis, leading to a reduction noradrenaline secretion. Notably, observed diminished neuronal patients with Alzheimer’s disease (AD) non-demented individuals type diabetes (T2D). cells, knockdown all including not only elevates phosphorylated tau but also cyclin-dependent kinase 5 (CDK5) expression, known promoter hyperphosphorylation accumulation tau, key pathological feature AD. Additionally, found prolonged exposure high glucose or cytokines markedly suggesting link between AD pathology metabolic stress through modulation these isoforms.

Язык: Английский

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Insulin signaling and oxidative stress: Bridging the gap between type 2 diabetes mellitus and Alzheimer's disease

Journal of Alzheimer s Disease, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Background Type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD) are two prevalent chronic diseases that pose significant global health challenges. Increasing evidence suggests a complex bidirectional relationship between these conditions, where T2D elevates the risk of AD, AD exacerbates glucose metabolism abnormalities in T2D. Objective This review explores molecular mechanisms linking focusing on role insulin signaling pathways oxidative stress. Methods A comprehensive literature search from PubMed, Web Science, other relevant databases was conducted analyzed. Results Insulin resistance leads to impaired brain, contributing cognitive decline development AD. Hyperglycemia-induced stress neuronal damage, promoting formation amyloid-β plaques neurofibrillary tangles characteristic Clinically antidiabetic drugs such as metformin show potential against preclinical studies; Many natural products Dendrobium nobile Lindl. have anti-T2D efficacy also effective various vivo vitro models. Conclusions Improving reducing important strategies treatment To understand bridging singling will provide insights broader applications alleviating

Язык: Английский

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Ceramide as a Promising Tool for Diagnosis and Treatment of Clinical Diseases: A Review of Recent Advances

Metabolites, Год журнала: 2025, Номер 15(3), С. 195 - 195

Опубликована: Март 11, 2025

Background/Objectives: Ceramide, a sphingolipid metabolite, has emerged as key player in various physiological and pathological processes. Changes ceramide levels are associated with the occurrence development of diseases, highlighting its potential biomarker clinical diseases. Methods: The biosynthesis metabolism discussed, along functions cell signaling, apoptosis, inflammation. This study further examines for disease diagnosis treatment. Results: article highlights involvement several including cardiovascular dermatosis, cancer, neurodegenerative disorders metabolic syndromes. For each disease, prognosis is explored, feasibility therapeutic strategies targeting reviewed. Additionally, challenges future directions field research addressed. Conclusions: review provides an overview recent advances understanding role diseases diagnostic tool.

Язык: Английский

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The neuroprotective role of Humanin in Alzheimer's disease: The molecular effects

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177510 - 177510

Опубликована: Март 1, 2025

Humanin (HN) is an endogenous micropeptide also known as a mitochondria-derived peptide. It has neuroprotective effect against Alzheimer's disease (AD) and other neurodegenerative diseases by improving hippocampal acetylcholine attenuating the development of oxidative stress associated neurotoxicity. HN protects neuron from toxic effects amyloid beta (Aβ). regarded biomarker mitochondrial stress. Interestingly, aging reduces brain expression HN, leading to cognitive impairment elevating risk neurodegeneration, including AD. However, in old subjects AD patients, circulating levels increase compensatory mechanism reduce neurodegeneration dysfunction Conversely, studies demonstrated reduction These findings indicated controversial points regarding precise mechanistic role Therefore, aim this review was discuss exact neuropathology molecular mechanisms

Язык: Английский

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The p66Shc Redox Protein and the Emerging Complications of Diabetes

International Journal of Molecular Sciences, Год журнала: 2023, Номер 25(1), С. 108 - 108

Опубликована: Дек. 20, 2023

Diabetes mellitus is a chronic metabolic disease, the prevalence of which constantly increasing worldwide. It often burdened by disabling comorbidities that reduce quality and expectancy life affected individuals. The traditional complications diabetes are generally described as macrovascular (e.g., coronary heart peripheral arterial stroke), microvascular diabetic kidney retinopathy, neuropathy). Recently, due to advances in management increased patients, strong correlation between other pathological conditions (such liver diseases, cancer, neurodegenerative cognitive impairments, sleep disorders) has emerged. Therefore, these have been proposed emerging diabetes. P66Shc redox protein plays role oxidative stress, apoptosis, glucose metabolism, cellular aging. can be regulated various stressful stimuli typical milieu involved types organ tissue damage under conditions. Although its pathogenesis remains controversial, there evidence regarding involvement p66Shc In this review, we will summarize supporting complications, focusing for first time on

Язык: Английский

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Methods to predict heart failure in diabetes patients

Expert Review of Endocrinology & Metabolism, Год журнала: 2024, Номер 19(3), С. 241 - 256

Опубликована: Апрель 13, 2024

Type 2 diabetes mellitus (T2DM) is one of the leading causes cardiovascular disease and powerful predictor for new-onset heart failure (HF).

Язык: Английский

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Improvement of Theaflavins on Glucose and Lipid Metabolism in Diabetes Mellitus

Foods, Год журнала: 2024, Номер 13(11), С. 1763 - 1763

Опубликована: Июнь 4, 2024

In diabetes mellitus, disordered glucose and lipid metabolisms precipitate diverse complications, including nonalcoholic fatty liver disease, contributing to a rising global mortality rate. Theaflavins (TFs) can improve disorders of glycolipid metabolism in diabetic patients reduce various types damage, glucotoxicity, lipotoxicity, other associated secondary adverse effects. TFs exert effects lower blood lipids levels, partly by regulating digestive enzyme activities, activation OATP-MCT pathway increasing secretion incretins such as GIP. By the Ca2+-CaMKK ꞵ-AMPK PI3K-AKT pathway, promote utilization inhibit endogenous production. Along with regulation energy AMPK-SIRT1 enhance acids oxidation de novo lipogenesis. As such, administration holds significant promise for both prevention amelioration mellitus.

Язык: Английский

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