Investigating the Effect and Mechanism of 3-Methyladenine Against Diabetic Encephalopathy by Network Pharmacology, Molecular Docking, and Experimental Validation DOI Creative Commons

Jiaxin Chu,

Jianqiang Song,

Zhonghang Fan

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(5), С. 605 - 605

Опубликована: Апрель 22, 2025

Background/Objectives: Diabetic encephalopathy (DE), a severe neurological complication of diabetes mellitus (DM), is characterized by cognitive dysfunction. 3-Methyladenine (3-MA), methylated adenine derivative, acts as biomarker for DNA methylation and exhibits hypoglycemic neuroprotective properties. However, the pharmacological mechanisms underlying 3-MA’s therapeutic effects on diabetic microvascular complications remain incompletely understood, owing to intricate multifactorial pathogenesis DE. Methods: This study employed network pharmacology molecular docking techniques predict potential targets signaling pathways 3-MA against DE, with subsequent validation through animal experiments elucidate in DE treatment. Results: Network analysis identified two key modulation: AKT GSK3β. Molecular confirmed strong binding affinity between AKT/GSK3β. In experiments, significantly reduced blood glucose levels mice, ameliorated learning memory deficits, preserved hippocampal neuronal integrity. Furthermore, we found that inhibited apoptosis regulating expression Bax BCL-2. Notably, also downregulated amyloid precursor protein (APP) Tau while enhancing phosphorylated GSK-3β. Conclusions: Our findings may contribute elucidating microangiopathy provide activation AKT/GSK-3β pathway.

Язык: Английский

Uncovering the intricacies of IGF-1 in Alzheimer’s disease: new insights from regulation to therapeutic targeting DOI

Navpreet Kaur,

Khadga Raj Aran

Inflammopharmacology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Язык: Английский

Процитировано

2
Modulating Neuroinflammation as a Prospective Therapeutic Target in Alzheimer’s Disease DOI Creative Commons

Eunshil Lee,

Yongmin Chang

Cells, Год журнала: 2025, Номер 14(3), С. 168 - 168

Опубликована: Янв. 22, 2025

The recent approval of lecanemab highlights that the amyloid beta (Aβ) protein is an important pathological target in Alzheimer’s disease (AD) and further emphasizes significance neuroinflammatory pathways regulating Aβ accumulation. Indeed, accumulation triggers microglia activation, which are key mediators neuroinflammation. inflammatory responses this process can lead to neuronal damage functional decline. Microglia secrete proinflammatory cytokines accelerate death release anti-inflammatory growth factors contributing recovery protection. Thus, play a dual role neurodegeneration neuroprotection, complicating their function AD. Therefore, elucidating complex interactions between protein, microglia, neuroinflammation essential for developing new strategies treating This review investigates receptors involved activating aims enhance understanding how these processes impact AD, as well they be regulated. also analyzed studies reported existing literature ongoing clinical trials. Overall, will contribute regulatory mechanisms therapies slow progression

Язык: Английский

Процитировано

1
Neuroprotective Effects of Dehydroepiandrosterone Sulphate Against Aβ Toxicity and Accumulation in Cellular and Animal Model of Alzheimer’s Disease DOI Creative Commons

Barbara Vuić,

Tina Milos,

Erika Kvak

и другие.

Biomedicines, Год журнала: 2025, Номер 13(2), С. 432 - 432

Опубликована: Фев. 11, 2025

Background/Objectives: Beneficial effects of neurosteroid dehydroepiandrosterone sulphate (DHEAS) on cognition, emotions and behavior have been previously reported, suggesting its potential in the prevention treatment various neuropsychiatric neurodegenerative disorders, including Alzheimer’s disease (AD). This study aimed to investigate neuroprotective actions DHEAS against Aβ toxicity both cellular animal models AD. Methods: After optimizing AD model vitro, we investigated viability death primary mouse neurons exposed toxic Aβ42 oligomers for 24 h. In order extend our research an vivo study, further tested acute intraperitoneal administration plaque density different brain regions 3xTg-AD mice, Results: cell culture, hampered decrease neuronal caused by oligomers, primarily influencing mitochondrial function apoptosis. also counteracted increase mRNA expression selected genes (PI3K, Akt, Bcl2, Bax), induced culture with oligomers. Obtained data suggested involvement mitochondria, caspases 3 7, as well PI3K/Akt Bcl2 signaling network antiapoptotic properties neurons. Forty-eight hours after treatment, a significantly lower number plaques was observed motor cortex but not other areas mice. Conclusions: Results indicated accumulation, that supplementation should be studied novel option and/or treatment.

Язык: Английский

Процитировано

1
Identification of critical genes and drug repurposing targets in entorhinal cortex of Alzheimer’s disease DOI
Arghavan Hosseinpouri, Khadijeh Sadegh, Zeinab Zarei‐Behjani

и другие.

Neurogenetics, Год журнала: 2025, Номер 26(1)

Опубликована: Фев. 10, 2025

Язык: Английский

Процитировано

0
Interplay between PI3k/AKT signaling and caspase pathway in Alzheimer disease: mechanism and therapeutic implications DOI
Vandana Bhatia, Vir Vikram Sharma, Abhimanyu Chandel

и другие.

Inflammopharmacology, Год журнала: 2025, Номер unknown

Опубликована: Март 15, 2025

Язык: Английский

Процитировано

0
Tricetin, a Dietary Flavonoid, Alleviates Neuroinflammation and Promotes Autophagy in Alzheimer’s Disease by Regulating the PI3K/Akt/mTOR Signaling Pathway DOI

Xinyuan Wu,

Dan Su, Jiaxin Xu

и другие.

Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 14, 2025

Alzheimer's disease (AD), the most prevalent neurodegenerative disorder among older adults, significantly impairs behavioral and cognitive functions, posing a severe threat to patients' health quality of life. The Tricetin (TRN), natural flavonoid found in wheat, pomegranate, eucalyptus honey, has demonstrated anti-inflammatory, antitumor, neuroprotective properties. However, its role context AD not been previously explored. This study investigated antineuroinflammatory autophagic protective effects TRN lipopolysaccharide (LPS)-induced BV2 cells D-galactose/sodium nitrite/aluminum chloride (D-gal/NaNO2/AlCl3)-induced mice. RNA sequencing examined underlying mechanisms by which ameliorates AD-related pathologies. Our research findings revealed that improved memory mobility mice, reduced Aβ deposition, inhibited Tau protein phosphorylation. Furthermore, regulated enzyme activities pathological markers associated with AD. Moreover, it modulated inflammatory mediators, nuclear translocation NF-κB LPS-induced cells, exerted anti-inflammatory via PI3K/Akt/mTOR signaling pathway. In conclusion, robust vitro vivo models regulating These highlight potential as promising therapeutic agent for treating

Язык: Английский

Процитировано

0
Investigating the Effect and Mechanism of 3-Methyladenine Against Diabetic Encephalopathy by Network Pharmacology, Molecular Docking, and Experimental Validation DOI Creative Commons

Jiaxin Chu,

Jianqiang Song,

Zhonghang Fan

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(5), С. 605 - 605

Опубликована: Апрель 22, 2025

Background/Objectives: Diabetic encephalopathy (DE), a severe neurological complication of diabetes mellitus (DM), is characterized by cognitive dysfunction. 3-Methyladenine (3-MA), methylated adenine derivative, acts as biomarker for DNA methylation and exhibits hypoglycemic neuroprotective properties. However, the pharmacological mechanisms underlying 3-MA’s therapeutic effects on diabetic microvascular complications remain incompletely understood, owing to intricate multifactorial pathogenesis DE. Methods: This study employed network pharmacology molecular docking techniques predict potential targets signaling pathways 3-MA against DE, with subsequent validation through animal experiments elucidate in DE treatment. Results: Network analysis identified two key modulation: AKT GSK3β. Molecular confirmed strong binding affinity between AKT/GSK3β. In experiments, significantly reduced blood glucose levels mice, ameliorated learning memory deficits, preserved hippocampal neuronal integrity. Furthermore, we found that inhibited apoptosis regulating expression Bax BCL-2. Notably, also downregulated amyloid precursor protein (APP) Tau while enhancing phosphorylated GSK-3β. Conclusions: Our findings may contribute elucidating microangiopathy provide activation AKT/GSK-3β pathway.

Язык: Английский

Процитировано

0