Inhibition of PTEN Attenuates Endoplasmic Reticulum Stress and Apoptosis via Activation of PI3K/AKT Pathway in Alzheimer’s Disease

Cui, Weigang; Wang, Songtao; Wang, Zhongping; Wang, Zhiyong; Sun, Chao; Zhang, Yinghua

doi:10.1007/s11064-017-2338-1

Cited by 68 publications

(53 citation statements)

References 47 publications

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“…Further, PTEN is a lipid and protein phosphatase that inhibits PI3/AKT signaling and inhibiting PTEN has neuroprotective effects in an AD mouse model, amyloid-β toxicity, a PD model, and lab models of spinal muscular atrophy [ 95 ]. PTEN inhibition has also been shown to reduce apoptosis and counteract ER-stress related proteins in an AD mouse model [ 96 ]. In contrast, however, PTEN overexpression seems to be neuroprotective in tauopathies [ 97 ].…”

Section: Dusps In Protein Aggregation Diseasesmentioning

confidence: 99%

Critical Roles of Dual-Specificity Phosphatases in Neuronal Proteostasis and Neurological Diseases

Bhore

Wang

Chen

et al. 2017

IJMS

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Protein homeostasis or proteostasis is a fundamental cellular property that encompasses the dynamic balancing of processes in the proteostasis network (PN). Such processes include protein synthesis, folding, and degradation in both non-stressed and stressful conditions. The role of the PN in neurodegenerative disease is well-documented, where it is known to respond to changes in protein folding states or toxic gain-of-function protein aggregation. Dual-specificity phosphatases have recently emerged as important participants in maintaining balance within the PN, acting through modulation of cellular signaling pathways that are involved in neurodegeneration. In this review, we will summarize recent findings describing the roles of dual-specificity phosphatases in neurodegeneration and offer perspectives on future therapeutic directions.

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Section: Dusps In Protein Aggregation Diseasesmentioning

confidence: 99%

Critical Roles of Dual-Specificity Phosphatases in Neuronal Proteostasis and Neurological Diseases

Bhore

Wang

Chen

et al. 2017

IJMS

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“…A study by Ling et al [30] has indicated that PI3K is a direct target of miR-320, and miR-320 could regulate the insulinresistant in 3T3-L1 adipocytes by targeting PI3K. Another study by Cui et al [47] reported that activation of PI3K/AKT signaling pathway attenuated ERs in Alzheimerʼs disease. Therefore, we suspect that miR-320 may promote ERs by directly regulation of PI3K.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR-320 Alleviates Endoplasmic Reticulum Stress and Inflammatory Response in 3T3-L1 Adipocytes

Liu

2019

Exp Clin Endocrinol Diabetes

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Objective MicroRNAs serve important roles in the regulation of endoplasmic reticulum stress (ERs). This study aimed to investigate the role of microRNA-320 (miR-320) in the development of ERs and the inflammatory response in 3T3-L1 adipocytes. Materials and Methods The adipose tissue expression levels of miR-320 and ERs markers (GRP78, GRP94, Derlin-1 and CHOP) and the serum concentration of inflammatory cytokines (TNF-α, NF-κB and IL-6) in obese patients were evaluated using quantitative real-time RT-PCR. The correlation of miR-320 with genes involved in ERs and inflammation was analyzed. The effects of miR-320 on ERs and inflammation were explored using mature 3T3-L1 adipocytes, which were pretreated with palmitic acid (PA). Results ERs markers and inflammatory cytokines were all upregulated in obese patients. Adipose tissue miR-320 expression was also increased in obese patients, and had positive correlations with the levels of ERs markers and inflammatory cytokines. After PA treatment, the levels of ERs markers and inflammatory cytokines were elevated significantly in 3T3-L1 adipocytes. Moreover, miR-320 expression was increased in the cells under ERs status. The upregulation of miR-320 could enhance the expression of ERs markers and inflammatory cytokines, but the downregulation of miR-320 resulted in the opposite results. Conclusion The data of this study indicate that miR-320 expression is upregulated in ERs status, and the downregulation of miR-320 ameliorates ERs and the inflammatory response in 3T3-L1 adipocytes. We consider that the approaches to decrease miR-320 expression may be novel therapeutic strategies for the treatment of obesity and obesity-related diseases.

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“…Alzheimer's disease ↑ GRP78 Aβ-treated SK-N-SH cells [203], RBE4 cells [204], Aβ 1-40 -treated RBE4 cells [205], Aβ 1-42 -treated bEnd.3 cells [206], 5XFAD mouse model [207], APP/PS1 transgenic mice [208], Aβ 1-42 -treated rat astrocytes, 3xTg-AD mice [209], mutant PS1 cells, 3xTg-AD mice [210]. ↓ GRP78 PS1 mutant SK-N-SH cells [211].…”

Section: Neurodegenerative Disease Upr Markers Experimental Modelmentioning

confidence: 99%

“…↑ CHOP Aβ-treated SK-N-SH cells [203], primary rat cortical neurons [212], RBE4 cells [204], temporal cortex of human AD brains [221], Aβ 1-40 -treated RBE4 cell line [205], Aβ 1-42 -treated bEnd.3 cells [206], 5XFAD mouse model [207], APP/PS1 transgenic mice [208]. ↑ GADD34 J20 mice [222], AD mouse model, human AD brains [223].…”

Section: Neurodegenerative Disease Upr Markers Experimental Modelmentioning

confidence: 99%

The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases

Rozpędek‐Kamińska

Siwecka

Wawrzynkiewicz

et al. 2020

IJMS

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Higher prevalence of neurodegenerative diseases is strictly connected with progressive aging of the world population. Interestingly, a broad range of age-related, neurodegenerative diseases is characterized by a common pathological mechanism—accumulation of misfolded and unfolded proteins within the cells. Under certain circumstances, such protein aggregates may evoke endoplasmic reticulum (ER) stress conditions and subsequent activation of the unfolded protein response (UPR) signaling pathways via the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent manner. Under mild to moderate ER stress, UPR has a pro-adaptive role. However, severe or long-termed ER stress conditions directly evoke shift of the UPR toward its pro-apoptotic branch, which is considered to be a possible cause of neurodegeneration. To this day, there is no effective cure for Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), or prion disease. Currently available treatment approaches for these diseases are only symptomatic and cannot affect the disease progression. Treatment strategies, currently under detailed research, include inhibition of the PERK-dependent UPR signaling branches. The newest data have reported that the use of small-molecule inhibitors of the PERK-mediated signaling branches may contribute to the development of a novel, ground-breaking therapeutic approach for neurodegeneration. In this review, we critically describe all the aspects associated with such targeted therapy against neurodegenerative proteopathies.

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Inhibition of PTEN Attenuates Endoplasmic Reticulum Stress and Apoptosis via Activation of PI3K/AKT Pathway in Alzheimer’s Disease

Cited by 68 publications

References 47 publications

Critical Roles of Dual-Specificity Phosphatases in Neuronal Proteostasis and Neurological Diseases

Critical Roles of Dual-Specificity Phosphatases in Neuronal Proteostasis and Neurological Diseases

Downregulation of miR-320 Alleviates Endoplasmic Reticulum Stress and Inflammatory Response in 3T3-L1 Adipocytes

The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases

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