Apoptosis in Alzheimer’s disease: insight into the signaling pathways and therapeutic avenues

APOPTOSIS, Journal Year: 2023, Volume and Issue: 28(7-8), P. 943 - 957

Published: April 26, 2023

Language: Английский

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The neuroprotective effects of glucagon-like peptide 1 in Alzheimer’s and Parkinson’s disease: An in-depth review

Frontiers in Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: Sept. 1, 2022

Currently, there is no disease-modifying treatment available for Alzheimer's and Parkinson's disease (AD PD) that includes the highly controversial approval of Aβ-targeting antibody aducanumab AD. Hence, still an unmet need a neuroprotective drug in both AD PD. Type 2 diabetes risk factor Glucagon-like peptide 1 (GLP-1) hormone growth has shown effects preclinical studies, success GLP-1 mimetics phase II clinical trials PD raised new hope. are currently on market as treatments type diabetes. analogs safe, well tolerated, resistant to desensitization characterized clinic. Herein, we review existing evidence illustrate pathways induced following GLP-1R activation neurons, microglia astrocytes. The latter include synaptic protection, improvements cognition, learning motor function, amyloid pathology-ameliorating properties (Aβ, Tau, α-synuclein), suppression Ca

Language: Английский

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Impairment of insulin signaling pathway PI3K/Akt/mTOR and insulin resistance induced AGEs on diabetes mellitus and neurodegenerative diseases: a perspective review

Molecular and Cellular Biochemistry, Journal Year: 2022, Volume and Issue: 478(6), P. 1307 - 1324

Published: Oct. 29, 2022

Language: Английский

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Environmental endocrine disruptor Bisphenol A induces metabolic derailment and obesity via upregulating IL-17A in adipocytes

Environment International, Journal Year: 2023, Volume and Issue: 172, P. 107759 - 107759

Published: Jan. 16, 2023

Bisphenol A (BPA), a ubiquitous environmental endocrine disruptor, has been extensively demonstrated to be associated with metabolic disorders, including obesity and type 2 diabetes mellitus. However, the underlying mechanism underpinning etiology of chronic disorders not sufficiently elucidated.This study is designed explore toxicological pathogenesis inflammation in BPA exposure during obesity.We investigated role IL-17A association from human cross-sectional animal models, genetically modified IL-17A-/- mice.Here, our work started case-control observation that was significantly risk (odds ratio = 4.72, 95%CI: 3.18 - 11.18, P < 0.01), disorder levels interleukin-17A (IL-17A) adipose (estimated changes β 0.46, 0.15 1.01, 0.01) bariatric surgery. Animal model fed high-fat diet (HFD) confirmed aggravated body weight gain insulin resistance, concurrent much heightened inflammatory responses tissue increase macrophage polarization towards M1 stage. Genetically ablated mice (IL-17A-/-) showed reversed response, improved homeostasis, along sensitivity both HFD group alone or more + group. Moreover, mediation analysis epidemiological investigation plasma attributed up 30.01% mediating associations between risk.This research paradigm provides strong evidence for elucidation moderating resistance obesity. Such findings reiterate obesogenic disruptor unveils potential mechanisms such effect.

Language: Английский

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Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 13, 2025

Abstract The pancreas, an organ with dual functions, regulates blood glucose levels through the endocrine system by secreting hormones such as insulin and glucagon. It also aids digestion exocrine digestive enzymes. Complex interactions signaling mechanisms between functions of pancreas play a crucial role in maintaining metabolic homeostasis overall health. Compelling evidence indicates direct indirect crosstalk parts, influencing development diseases affecting both. From developmental perspective, parts share same origin—the “tip-trunk” domain. In certain circumstances, pancreatic cells may transdifferentiate into endocrine-like cells, insulin-secreting cells. Additionally, several diseases, including cancer, pancreatitis, diabetes, exhibit potential relevance to both functions. Endocrine communicate directly cytokines or indirectly regulating immune microenvironment. This affects onset progression these diseases. review summarizes history milestones findings related their embryonic development, phenotypic transformations, roles health disease, endocrine-exocrine from perspective therapeutic targets. Elucidating regulatory provide novel insights for understanding treatment

Language: Английский

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Type 2 Diabetes Mellitus Exacerbates Pathological Processes of Parkinson's Disease: Insights from Signaling Pathways Mediated by Insulin Receptors

Neuroscience Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Language: Английский

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Mitochondrial Dysfunction in Alzheimer’s Disease

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102713 - 102713

Published: Feb. 1, 2025

Language: Английский

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Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in the Brain and Relevance for Neuropsychiatric Disorders

Frontiers in Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: June 12, 2020

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has long been studied in the liver due to its regulation of plasma low-density lipoprotein cholesterol (LDL-C) and causal role familial hypercholesterolemia. Although PCSK9 was first discovered cerebellar neurons undergoing apoptosis, function central nervous system is less clear. shown be involved neuronal differentiation, LDL receptor family metabolism, apoptosis inflammation brain, but vitro vivo studies offer contradictory findings. expression adult brain low highly upregulated during disease states. Cerebral spinal fluid (CSF) concentrations are correlated with neural tube defects neurodegenerative diseases human patients. Epigenetic reveal that chronic alcohol use may modulate methylation gene genetic show patients gain-of-function variants have higher LDL-C an increased risk ischemic stroke. Early safety inhibitors evolocumab alirocumab, used treat hypercholesterolemia, hinted inhibition negatively impact cognition more recent, longer-term clinical trials found no adverse neurocognitive events. The purpose this review elucidate particularly pathogenesis.

Language: Английский

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Incretin and insulin signaling as novel therapeutic targets for Alzheimer’s and Parkinson’s disease

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 28(1), P. 217 - 229

Published: Oct. 18, 2022

Abstract Despite an ever-growing prevalence and increasing economic burden of Alzheimer’s disease (AD) Parkinson’s (PD), recent advances in drug development have only resulted minimally effective treatment. In AD, along with amyloid tau phosphorylation, there is associated increase inflammation/glial activation, a decrease synaptic function, astrocyte state insulin resistance. PD, α-synuclein accumulation, inflammation, dysfunction, dopaminergic neuronal loss, some data to suggest Therapeutic strategies for neurodegenerative disorders commonly targeted individual pathological processes. An treatment might require either utilization multiple drugs which target the processes underlie or use single agent could influence Insulin incretins are compounds effects on Preclinical studies demonstrated that GLP-1 receptor agonists reduce neuroinflammation, deposition, improve memory formation. Incretin mimetics may act through restoration signaling pathways, inducing further neuroprotective effects. Currently, phase 2 3 trials underway AD PD populations. Here, we provide comprehensive review therapeutic potential incretin PD.

Language: Английский

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Insulin resistance, autophagy and apoptosis in patients with polycystic ovary syndrome: Association with PI3K signaling pathway

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 16, 2022

Polycystic ovary syndrome (PCOS) is a disease in which endocrine metabolic abnormalities coexist with reproductive system abnormalities, the main clinical manifestations including abnormal menstruation, hirsutism, acne, infertility, and obesity, it also high risk for development of many pregnancy complications, gynecological malignancies other diseases. Therefore, timely intervention to prevent progression PCOS great significance improving quality life most female patients. Insulin resistance (IR) one common disorders patients, approximately 75% patients experiencing varying degrees IR. It now believed that mainly related PI3K signaling pathway. The role autophagy apoptosis ovarian granulosa cells (GCs) pathogenesis has been gradually verified recent years. Coincidentally, seems be associated Our aim review these relevant studies, explore association between IR, cellular We summarize some drug studies have improved as well. found proteomics holds promise exploring PCOS, we published our views on this.

Language: Английский

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