Recent Advances of Mitochondrial Alterations in Alzheimer’s Disease: A Perspective of Mitochondrial Basic Events DOI
Wenyan Wei, Ying Jiang,

Guizhen Hu

et al.

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 101(2), P. 379 - 396

Published: Aug. 27, 2024

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders and characterized by a decrease in learning capacity, memory loss behavioral changes. In addition to well-recognized amyloid-β cascade hypothesis hyperphosphorylated Tau hypothesis, accumulating evidence has led proposal mitochondrial dysfunction as primary etiology AD. However, predominant molecular mechanisms underlying development progression AD have not been fully elucidated. Mitochondrial only considered an early event pathogenesis but also involved whole course disease, with numerous pathophysiological processes, including disordered energy metabolism, Ca2+ homeostasis hyperactive oxidative stress. current review, we integrated emerging summarize main alterations- bioenergetic inheritance, mitobiogenesis, fission- fusion dynamics, degradation, movement- pathogenesis; precisely identified regulators; discussed potential processes; highlighted leading players; noted additional incidental signaling pathway This review may help stimulate research exploring metabolically-oriented neuroprotection strategies therapies, better understanding link between pathogenesis.

Language: Английский

Antidiabetic agents as a novel treatment for Alzheimer’s and Parkinson’s disease DOI Creative Commons

Joseph Nowell,

Eleanor G Blunt, Dhruv Gupta

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 89, P. 101979 - 101979

Published: June 15, 2023

Therapeutic strategies for neurodegenerative disorders have commonly targeted individual aspects of the disease pathogenesis to little success. Neurodegenerative diseases, including Alzheimer's (AD) and Parkinson's (PD), are characterized by several pathological features. In AD PD, there is an abnormal accumulation toxic proteins, increased inflammation, decreased synaptic function, neuronal loss, astrocyte activation, perhaps a state insulin resistance. Epidemiological evidence has revealed link between AD/PD type 2 diabetes mellitus, with these sharing some commonalities. Such opened up promising avenue repurposing antidiabetic agents in treatment disorders. A successful therapeutic strategy would likely require single or which target separate processes disease. Targeting cerebral signalling produces numerous neuroprotective effects preclinical brain models. Clinical trials shown promise approved diabetic compounds improving motor symptoms PD preventing decline, further phase II III underway populations. Alongside signalling, targeting incretin receptors represents one most currently available AD/PD. Most notably, glucagon-like-peptide-1 (GLP-1) receptor agonists displayed impressive clinical potential early studies. GLP-1 agonist, liraglutide, been demonstrated improve glucose metabolism functional connectivity small-scale pilot trials. Whilst agonist exenatide effective restoring function cognition. reduces inhibits apoptosis, prevents protein aggregation, enhances long-term potentiation autophagy as well restores dysfunctional signalling. Support also increasing use additional treatments, intranasal insulin, metformin hydrochloride, peroxisome proliferator-activated nuclear γ agonists, amylin analogs, tyrosine phosphatase 1B inhibitors investigation deployment treatment. As such, we provide comprehensive review anti-diabetic PD.

Language: Английский

Citations

84
Unveiling the interplay of AMPK/SIRT1/PGC-1α axis in brain health: Promising targets against aging and NDDs DOI
Pratik Shankar Rakshe, Bhaskar Jyoti Dutta, Shivani Chib

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102255 - 102255

Published: March 14, 2024

Language: Английский

Citations

29
Exploring the Therapeutic Role of Flavonoids Through AMPK Activation in Metabolic Syndrome: A Narrative Review DOI Open Access

Lunasmrita Saikia,

Narayan Chandra Talukdar, Partha Dutta

et al.

Phytotherapy Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

ABSTRACT Metabolic syndrome (MetS) is a cluster of interrelated metabolic abnormalities that significantly elevate the risk cardiovascular disease, obesity, and diabetes. Flavonoids, diverse class bioactive polyphenolic compounds found in plant‐derived foods beverages, have garnered increasing attention as potential therapeutic agents for improving health. This review provides comprehensive analysis effects flavonoids context MetS, with particular focus on their modulation AMP‐activated protein kinase (AMPK) pathway. AMPK serves central regulator cellular energy balance, glucose metabolism, lipid homeostasis, making it critical target intervention. Through systematic literature up to April 2024, preclinical studies across various flavonoid subclasses, including flavonols, flavan‐3‐ols, were analysed elucidate mechanistic roles regulation. Many suggests enhance glycolipid metabolism by facilitating transporter 4 (GLUT4) translocation activating pathway, thereby glycemic control diabetes models. In obesity‐related studies, demonstrated significant inhibitory synthesis, reduced adipogenesis, attenuated proinflammatory cytokine secretion via activation. These findings show broad addressing MetS its associated disorders. While these insights highlight promising natural health improvement, important note excessive concentrations may disrupt pathways, potentially leading imbalance cytotoxicity. Further clinical trials are essential determine optimal dosing regimens, formulations, long‐term safety efficacy flavonoids. highlights importance interventions targeting comorbidities, offering foundation future translational research.

Language: Английский

Citations

2
The GLP-1 Agonist Semaglutide Ameliorates Cognitive Regression in P301S Tauopathy Mice Model via Autophagy/ACE2/SIRT1/FOXO1-Mediated Microglia Polarization DOI
Norhan N. Elbadawy, Muhammed A. Saad, Sara Elfarrash

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177305 - 177305

Published: Jan. 1, 2025

Language: Английский

Citations

2
Neuroprotective potential of Erigeron bonariensis ethanolic extract against ovariectomized/D-galactose-induced memory impairments in female rats in relation to its metabolite fingerprint as revealed using UPLC/MS DOI Creative Commons
Weam W. Ibrahim,

Rabab H. Sayed,

Mohamed F. Abdelhameed

et al.

Inflammopharmacology, Journal Year: 2024, Volume and Issue: 32(2), P. 1091 - 1112

Published: Jan. 31, 2024

Abstract Erigeron bonariensis is widely distributed throughout the world's tropics and subtropics. In folk medicine, E. has historically been used to treat head brain diseases. Alzheimer’s disease (AD) most widespread form of dementia initiated via disturbances in function. Herein, neuroprotective effect chemically characterized ethanolic extract reported for first time an AD animal model. Chemical profiling was conducted using UPLC–ESI-MS analysis. Female rats underwent ovariectomy (OVX) followed by 42 days D-galactose (D-Gal) administration (150 mg/kg/day, i.p) induce AD. The OVX/D-Gal-subjected received either donepezil (5 mg/kg/day) or at 50, 100, 200 given 1 h prior D-Gal. analysis identified chemicals, including flavonoids, phenolic acids, terpenes, nitrogenous constituents. Several metabolites, such as isoschaftoside, casticin, velutin, pantothenic acid, xanthurenic C18-sphingosine, linoleamide, erucamide, were herein genus. Treatment with mitigated cognitive decline Morris Water Maze test histopathological alterations cortical hippocampal tissues rats. Moreover, OVX/D-Gal-induced Aβ aggregation, Tau hyperphosphorylation, AChE activity, neuroinflammation (NF-κBp65, TNF-α, IL-1β), apoptosis (Cytc, BAX). Additionally, ameliorated increasing α7-nAChRs expression, down-regulating GSK-3β FOXO3a modulating Jak2/STAT3/NF-ĸB p65 PI3K/AKT signaling cascades. These findings demonstrate memory-enhancing effects OVX/D-Gal rat model, highlighting its potential a promising candidate management. Graphical

Language: Английский

Citations

9
Repurposing antidiabetic drugs for Alzheimer's disease: A review of preclinical and clinical evidence and overcoming challenges DOI

Jacky Tran,

Sneh Parekh,

Julia Rockcole

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 355, P. 123001 - 123001

Published: Aug. 22, 2024

Language: Английский

Citations

9
Drugs repurposing in the experimental models of Alzheimer’s disease DOI Creative Commons

Sheer A. Joodi,

Weam W. Ibrahim, Mahmoud M. Khattab

et al.

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Abstract The currently approved drugs for Alzheimer’s disease (AD) are only symptomatic treatment in the early stages of but they could not halt neurodegeneration, additionally, safety profile recently developed immunotherapy is a big issue. This review aims to explain importance repurposing technique and strategy develop therapy AD. We illustrated biological alterations pathophysiology AD including amyloid pathology, Tau oxidative stress, mitochondrial dysfunction, neuroinflammation, glutamate-mediated excitotoxicity, insulin signaling impairment, wingless-related integration site/ β -catenin signaling, autophagy. Additionally, we demonstrated different repurposed experimental models anti-inflammatory, anti-hypertensive, anti-diabetic, antiepileptic, antidepressant anticancer drugs. Further, showed pipeline FDA have promising therapeutic activity against AD, confirming value elucidate curative Graphical abstract

Language: Английский

Citations

1
Danshensu sodium salt alleviates muscle atrophy via CaMKII‐PGC1α‐FoxO3a signaling pathway in D‐galactose‐induced models DOI Creative Commons
Pooreum Lim, Seung-Hwan Woo, JiHye Han

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(2)

Published: Jan. 21, 2025

Abstract Sarcopenia is an age‐related muscle atrophy syndrome characterized by the loss of strength and mass. Although many agents have been used to treat sarcopenia, there are no successful treatments date. In this study, we identified Danshensu sodium salt (DSS) as a substantial suppressive agent atrophy. We D‐galactose (DG)‐induced aging‐acceleration model, both in vivo vitro, confirm effect DSS on sarcopenia. inhibits expression atrophy‐related factors (MuRF1, MAFbx, myostatin, FoxO3a) DG‐induced mouse C2C12 human skeletal cells. Additionally, restored diameter reduced myotubes. Next, demonstrated that stimulates AMPK PGC1α through CaMKII. translocation FoxO3a into nucleus, thus inhibiting calcium‐dependent manner. initiated protein–protein interaction between PGC1α. The reduction PGC1α‐FoxO3a DG was DSS. Also, suppressed increased intracellular reactive oxygen species (ROS) DG. animal models, administration improved mass physical performance (grip hanging test) under accelerated aging conditions. These findings attenuates factors. Therefore, may be potential therapeutic for treatment

Language: Английский

Citations

1
NLRP3 inflammasome inhibition and M1-to-M2 microglial polarization shifting via scoparone-inhibited TLR4 axis in ovariectomy/D-galactose Alzheimer's disease rat model DOI
Weam W. Ibrahim, Krystyna Skalicka‐Woźniak, Barbara Budzyńska

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 119, P. 110239 - 110239

Published: May 1, 2023

Language: Английский

Citations

23
Dapagliflozin Ameliorates Cognitive Impairment in Aluminum-Chloride-Induced Alzheimer’s Disease via Modulation of AMPK/mTOR, Oxidative Stress and Glucose Metabolism DOI Creative Commons

Waad A. Samman,

Salma Selim,

Hassan M. El Fayoumi

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(5), P. 753 - 753

Published: May 16, 2023

Alzheimer's disease (AD) is a progressive neurological illness characterized by memory loss and cognitive deterioration. Dapagliflozin was suggested to attenuate the impairment associated with AD; however, its mechanisms were not fully elucidated. This study aims examine possible of neuroprotective effects dapagliflozin against aluminum chloride (AlCl3)-induced AD. Rats distributed into four groups: group 1 received saline, 2 AlCl3 (70 mg/kg) daily for 9 weeks, groups 3 4 administered 5 weeks. (1 (5 then given another Two behavioral experiments performed: Morris Water Maze (MWM) Y-maze spontaneous alternation (Y-maze) task. Histopathological alterations in brain, as well changes acetylcholinesterase (AChE) amyloid β (Aβ) peptide activities oxidative stress (OS) markers, all evaluated. A western blot analysis used detection phosphorylated 5' AMP-activated protein kinase (p-AMPK), mammalian target Rapamycin (p-mTOR) heme oxygenase-1 (HO-1). Tissue samples collected isolation glucose transporters (GLUTs) glycolytic enzymes using PCR analysis, brain levels also measured. The current data demonstrate that represents approach combat AlCl3-induced AD rats through inhibiting stress, enhancing metabolism activating AMPK signaling.

Language: Английский

Citations

20