P2‐021: Metformin and Topiramate Improve Learning and Memory in Diabetic Mice and Samp8 Mice Model of Alzheimer's Disease

Morley, John E.; Niehoff, Michael L.; Bergin, Michael W.; Roesler, Elizabeth C.; Shah, Gul N.; Price, Tulin O.; Farr, Susan A.

doi:10.1016/j.jalz.2014.05.694

Cited by 2 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The antioxidant properties of metformin may clarify the new pharmacological transduction pathways of this medicine via the regulation of redox dependence. Studies have shown that metformin can improve cognitive ability in a mouse model of Alzheimer's disease [23,24]. These results indicate that metformin may have a protective effect in neurological diseases caused by neuronal damage.…”

Section: Introductionmentioning

confidence: 83%

Metformin Protects against Oxidative Stress Injury Induced by Ischemia/Reperfusion via Regulation of the lncRNA-H19/miR-148a-3p/Rock2 Axis

Zeng

Zhu

Liu

et al. 2019

Oxidative Medicine and Cellular Longevity

107

View full text Add to dashboard Cite

Previous studies have shown that metformin not only is a hypoglycemic agent but also has neuroprotective effects. However, the mechanism of action of metformin in ischemic stroke is unclear. Oxidative stress is an important factor in the pathogenesis of cerebral ischemia-reperfusion injury. It has been reported that metformin is associated with stroke risk in the clinical population. This study is aimed at investigating the effect and mechanism of metformin in an experimental model of oxidative stress induced by ischemia/reperfusion (I/R) in vivo and oxygen glucose deprivation/reperfusion (OGD/R) in vitro. Metformin (100, 200, and 300 mg/kg) was administered intraperitoneally immediately after induction of cerebral ischemia. The indicators of oxidative stress selected were antioxidant enzyme activities of catalase, malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione peroxidation enzyme (GSHPx). First, we demonstrated that metformin can significantly alleviate acute and chronic cerebral I/R injury and it has a strong regulatory effect on stroke-induced oxidative stress. It can reduce the elevated activities of MDA and NO and increase the levels of GSHPx and SOD in the cerebrum of mice and N2a cells exposed to I/R. Furthermore, real-time PCR and western blot were used to detect the expression of long noncoding RNA H19 (lncRNA-H19), microRNA-148a-3p (miR-148a-3p), and Rho-associated protein kinase 2 (Rock2). The direct interaction of lncRNA-H19, miR-148a-3p, and Rock2 was tested using a dual luciferase reporter assay. lncRNA-H19 altered OGD/R-induced oxidative stress by modulating miR-148a-3p to increase Rock2 expression. The expression of lncRNA-H19 and Rock2 could be downregulated with metformin in vivo and in vitro. In conclusion, our study confirmed that metformin exerts neuroprotective effects by regulating ischemic stroke-induced oxidative stress injury via the lncRNA-H19/miR-148a-3p/Rock2 axis. These results provide new evidence that metformin may represent a potential treatment for stroke-related brain injury.

show abstract

Section: Introductionmentioning

confidence: 83%

Metformin Protects against Oxidative Stress Injury Induced by Ischemia/Reperfusion via Regulation of the lncRNA-H19/miR-148a-3p/Rock2 Axis

Zeng

Zhu

Liu

et al. 2019

Oxidative Medicine and Cellular Longevity

107

View full text Add to dashboard Cite

show abstract

Pharmacological Interventions to Attenuate Alzheimer’s Disease Progression: The Story So Far

Bazzari

Abdallah

El‐Abhar

2019

CAR

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia in the elderly. Up to date, the available pharmacological options for AD are limited to cholinesterase inhibitors and memantine that may only provide modest symptomatic management with no significance in slowing down the disease progression. Over the past three decades, the increased interest in and the understanding of AD major pathological hallmarks have provided an insight into the mechanisms mediating its pathogenesis, which in turn introduced a number of hypotheses and novel targets for the treatment of AD. Initially, targeting amyloid-beta and tau protein was considered the most promising therapeutic approach. However, further investigations have identified other major players, such as neuroinflammation, impaired insulin signalling and defective autophagy, that may contribute to the disease progression. While some promising drugs are currently being investigated in human studies, the majority of the previously developed medical agents have come to an end in clinical trials, as they have failed to illustrate any beneficial outcome. This review aims to discuss the different introduced approaches to alleviate AD progression; in addition, provides a comprehensive overview of the drugs in the development phase as well as their mode of action and an update of their status in clinical trials.

show abstract

P2‐021: Metformin and Topiramate Improve Learning and Memory in Diabetic Mice and Samp8 Mice Model of Alzheimer's Disease

Cited by 2 publications

References 0 publications

Metformin Protects against Oxidative Stress Injury Induced by Ischemia/Reperfusion via Regulation of the lncRNA-H19/miR-148a-3p/Rock2 Axis

Metformin Protects against Oxidative Stress Injury Induced by Ischemia/Reperfusion via Regulation of the lncRNA-H19/miR-148a-3p/Rock2 Axis

Pharmacological Interventions to Attenuate Alzheimer’s Disease Progression: The Story So Far

Contact Info

Product

Resources

About