Metformin alleviates high glucose-induced ER stress and inflammation by inhibiting the interaction between caveolin1 and AMPKα in rat astrocytes

Wang, Gang; Chen, Wei; Chen, Shurui; Shao, Zhenya; Li, Yankun; Wang, Wei; Mao, Liang; Li, Jian; Mei, Xifan

doi:10.1016/j.bbrc.2020.10.075

Cited by 27 publications

(17 citation statements)

References 25 publications

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“…In rats with scopolamine-induced cognitive impairment, metformin decreased the level of nitric oxide (NO) and MDA in the frontal cortical and hippocampal tissues ( Mostafa et al, 2016 ). Metformin was also found to inhibit the elevated levels of inflammation and endoplasmic reticulum (ER) stress by high glucose treatment through suppressing the interaction between AMPKα and caveolin1 in primary rat astrocytes ( Wang et al, 2021 ).…”

Section: Mechanisms Linking Metformin With Admentioning

confidence: 99%

Deciphering the Roles of Metformin in Alzheimer’s Disease: A Snapshot

Ruan

et al. 2022

Front. Pharmacol.

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Alzheimer’s disease (AD) is a prevalent neurodegenerative disease predominantly affecting millions of elderly people. To date, no effective therapy has been identified to reverse the progression of AD. Metformin, as a first-line medication for Type 2 Diabetes Mellitus (T2DM), exerts multiple beneficial effects on various neurodegenerative disorders, including AD. Evidence from clinical studies has demonstrated that metformin use contributes to a lower risk of developing AD and better cognitive performance, which might be modified by interactors such as diabetic status and APOE-ε4 status. Previous mechanistic studies have gradually unveiled the effects of metformin on AD pathology and pathophysiology, including neuronal loss, neural dysfunction, amyloid-β (Aβ) depositions, tau phosphorylation, chronic neuroinflammation, insulin resistance, impaired glucose metabolism and mitochondrial dysfunction. Current evidence remains ambiguous and even conflicting. Herein, we review the current state of knowledge concerning the mechanisms of metformin in AD pathology while summarizing current evidence from clinical studies.

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Section: Mechanisms Linking Metformin With Admentioning

confidence: 99%

Deciphering the Roles of Metformin in Alzheimer’s Disease: A Snapshot

Ruan

et al. 2022

Front. Pharmacol.

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“…Metformin is well known to activate AMPK in different tissues in humans and rodents [ 88 , 89 , 90 ]. The effects of metformin on endothelial function are largely mediated through AMPK and PPARδ with a subsequent alleviation of ER stress and oxidative stress as well as increased eNOS activity and NO production, highlighting the central role of PPARδ downstream of AMPK activation to combat against diabetes- and obesity-related vasculopathy, inflammation and hypertension [ 91 , 92 , 93 ]. Likewise, exercise is known to activate AMPK and is found to ameliorate ER stress and endothelial dysfunction in diabetes through PPARδ [ 94 ].…”

Section: Er Stress Linking To Cardiovascular Complications In Diabetes and Obesitymentioning

confidence: 99%

Roles and Therapeutic Implications of Endoplasmic Reticulum Stress and Oxidative Stress in Cardiovascular Diseases

et al. 2021

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In different pathological states that cause endoplasmic reticulum (ER) calcium depletion, altered glycosylation, nutrient deprivation, oxidative stress, DNA damage or energy perturbation/fluctuations, the protein folding process is disrupted and the ER becomes stressed. Studies in the past decade have demonstrated that ER stress is closely associated with pathogenesis of obesity, insulin resistance and type 2 diabetes. Excess nutrients and inflammatory cytokines associated with metabolic diseases can trigger or worsen ER stress. ER stress plays a critical role in the induction of endothelial dysfunction and atherosclerosis. Signaling pathways including AMP-activated protein kinase and peroxisome proliferator-activated receptor have been identified to regulate ER stress, whilst ER stress contributes to the imbalanced production between nitric oxide (NO) and reactive oxygen species (ROS) causing oxidative stress. Several drugs or herbs have been proved to protect against cardiovascular diseases (CVD) through inhibition of ER stress and oxidative stress. The present article reviews the involvement of ER stress and oxidative stress in cardiovascular dysfunction and the potential therapeutic implications.

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“…Taken together, these results seem to underly the beneficial effect of metformin in reducing neuroinflammation, highlighting the importance of increasing the efforts in this research field to understand more in detail how the drug exerts the anti-inflammatory activity. Noteworthy, also the effects on microglial cells might be related to the activation of AMPK, which has been linked to the anti-inflammatory pathway, suggesting that the activation of the AMPK pathway may account for many of the effects ascribed to metformin [ 17 , 54 , 64 ].…”

Section: Potential Neuroprotective Mechanisms Of Action Of Metforminmentioning

confidence: 99%

Metformin Repurposing for Parkinson Disease Therapy: Opportunities and Challenges

Agostini

Masato

Bubacco

et al. 2021

IJMS

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Parkinson disease (PD) is a severe neurodegenerative disorder that affects around 2% of the population over 65 years old. It is characterized by the progressive loss of nigrostriatal dopaminergic neurons, resulting in motor disabilities of the patients. At present, only symptomatic cures are available, without suppressing disease progression. In this frame, the anti-diabetic drug metformin has been investigated as a potential disease modifier for PD, being a low-cost and generally well-tolerated medication, which has been successfully used for decades in the treatment of type 2 diabetes mellitus. Despite the precise mechanisms of action of metformin being not fully elucidated, the drug has been known to influence many cellular pathways that are associated with PD pathology. In this review, we present the evidence in the literature supporting the neuroprotective role of metformin, i.e., autophagy upregulation, degradation of pathological α-synuclein species, and regulation of mitochondrial functions. The epidemiological studies conducted in diabetic patients under metformin therapy aimed at evaluating the correlation between long-term metformin consumption and the risk of developing PD are also discussed. Finally, we provide an interpretation for the controversial results obtained both in experimental models and in clinical studies, thus providing a possible rationale for future investigations for the repositioning of metformin for PD therapy.

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Metformin alleviates high glucose-induced ER stress and inflammation by inhibiting the interaction between caveolin1 and AMPKα in rat astrocytes

Cited by 27 publications

References 25 publications

Deciphering the Roles of Metformin in Alzheimer’s Disease: A Snapshot

Deciphering the Roles of Metformin in Alzheimer’s Disease: A Snapshot

Roles and Therapeutic Implications of Endoplasmic Reticulum Stress and Oxidative Stress in Cardiovascular Diseases

Metformin Repurposing for Parkinson Disease Therapy: Opportunities and Challenges

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