Dysregulated mTOR networks in experimental sporadic Alzheimer’s disease DOI Creative Commons
Suzanne M. de la Monte, Ming Tong

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Сен. 25, 2024

Beyond the signature amyloid-beta plaques and neurofibrillary tangles, Alzheimer's disease (AD) has been shown to exhibit dysregulated metabolic signaling through insulin insulin-like growth factor (IGF) networks that crosstalk with mechanistic target of rapamycin (mTOR). Its broad impact on brain structure function suggests mTOR is likely an important therapeutic for AD. This study characterizes temporal lobe (TL) abnormalities in a rat model sporadic AD neurodegeneration. Long Evans rats were given intracerebroventricular injections streptozotocin (ic-STZ) or saline (control), 4 weeks later, they administered neurobehavioral tests followed by terminal harvesting TLs histopathological measurement biomarkers, neuroinflammatory/oxidative stress markers, total phosphorylated insulin/IGF-1-Akt-mTOR pathway molecules. Rats treated ic-STZ exhibited significantly impaired performance Rotarod (RR) Morris Water Maze (MWM) tests, atrophy, TL hippocampal neuronal white matter degeneration, elevated pTau, AβPP, Aβ, AChE, 4-HNE, GAPDH reduced ubiquitin, IL-2, IL-6, IFN-γ immunoreactivities. In addition, pY1135/1136-IGF-1R, Akt, PTEN, pS380-PTEN, pS2448-mTOR, p70S6K, pT412-p70S6K, p/T-pT412-p70S6K, p/T-Rictor, p/T-Raptor. Experimental ic-STZ-induced AD-type neurodegeneration dysfunctions associated inhibition linked energy metabolism, plasticity, integrity.

Язык: Английский

IRS gene polymorphisms in Turkish patients with late-onset Alzheimer’s disease DOI
Hülya Özkan, Mustafa Yıldız, Ayten Üstündağ

и другие.

Molecular Biology Reports, Год журнала: 2025, Номер 52(1)

Опубликована: Фев. 15, 2025

Язык: Английский

Процитировано

0
Opposite causal effects of type 2 diabetes and metformin on Alzheimer's disease DOI Creative Commons
Dongming Liu, Hongbao Cao, Ancha Baranova

и другие.

The Journal of Prevention of Alzheimer s Disease, Год журнала: 2025, Номер unknown, С. 100129 - 100129

Опубликована: Март 1, 2025

Type 2 diabetes (T2D) is commonly co-morbid with Alzheimer's disease (AD). However, it remains unclear whether T2D itself or the antidiabetic drug metformin contributes to progression of AD. This study aimed investigate overall and independent effects use on risk Summary genome-wide association datasets were utilized for Mendelian randomization (MR) multivariable MR (MVMR) analyses, including ones (N = 455,017), 456,276), AD 453,733). Additionally, using proportional imbalance method, we analyzed AD-related adverse events in FDA Adverse Event Reporting System (FAERS) database (covering Q1 2004 Q2 2024). Our two-sample analysis indicated that not associated (OR: 1.03, CI: 0.99-1.08, P 0.128). while statistically significant, genetic signature exposure demonstrated a trend toward an increased 1.05, 1.00-1.09, 0.053). Interestingly, MVMR analysis, which evaluates T2D, found robust decrease 0.82, 0.68-0.98, 0.031), was higher 1.26, 1.06-1.50, 9.45E-3). In FAERS database, total 228,283 metformin-related event reports from 67,742 cases found. For as target event, signal reported 29 (ROR: 0.83, 95 % 0.58-1.19, 0.3126). reveals opposite causal These findings highlight importance assessing when prescribing patients T2D.

Язык: Английский

Процитировано

0
Dysregulated mTOR networks in experimental sporadic Alzheimer’s disease DOI Creative Commons
Suzanne M. de la Monte, Ming Tong

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Сен. 25, 2024

Beyond the signature amyloid-beta plaques and neurofibrillary tangles, Alzheimer's disease (AD) has been shown to exhibit dysregulated metabolic signaling through insulin insulin-like growth factor (IGF) networks that crosstalk with mechanistic target of rapamycin (mTOR). Its broad impact on brain structure function suggests mTOR is likely an important therapeutic for AD. This study characterizes temporal lobe (TL) abnormalities in a rat model sporadic AD neurodegeneration. Long Evans rats were given intracerebroventricular injections streptozotocin (ic-STZ) or saline (control), 4 weeks later, they administered neurobehavioral tests followed by terminal harvesting TLs histopathological measurement biomarkers, neuroinflammatory/oxidative stress markers, total phosphorylated insulin/IGF-1-Akt-mTOR pathway molecules. Rats treated ic-STZ exhibited significantly impaired performance Rotarod (RR) Morris Water Maze (MWM) tests, atrophy, TL hippocampal neuronal white matter degeneration, elevated pTau, AβPP, Aβ, AChE, 4-HNE, GAPDH reduced ubiquitin, IL-2, IL-6, IFN-γ immunoreactivities. In addition, pY1135/1136-IGF-1R, Akt, PTEN, pS380-PTEN, pS2448-mTOR, p70S6K, pT412-p70S6K, p/T-pT412-p70S6K, p/T-Rictor, p/T-Raptor. Experimental ic-STZ-induced AD-type neurodegeneration dysfunctions associated inhibition linked energy metabolism, plasticity, integrity.

Язык: Английский

Процитировано

1