Illite improves memory impairment and reduces Aβ level in the Tg-APPswe/PS1dE9 mouse model of Alzheimer׳s disease through Akt/CREB and GSK-3β phosphorylation in the brain

Jeon, Songhee; Park, Jeong Eun; Lee, Jin‐Hee; Liu, Quan Feng; Jeong, Hana; Pak, Sok Cheon; Yi, Sudok; Kim, Myung Hun; Kim, Chan Wha; Park, Jung Keug; Kim, Geun Woo; Koo, Byung Soo

doi:10.1016/j.jep.2014.11.029

Cited by 15 publications

(7 citation statements)

References 45 publications

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“…Further downstream, CREB is one of the key substrates of PI3K/Akt signaling, and is closely related to cell survival and neuroprotection. 23 In addition, CREB activation leads to the gene expression of neuroprotective molecules such as the antiapoptotic protein bcl-2, and thus contributes to neuronal survival. 24 Increased bcl-2 inhibits the activation of caspase-3, safeguarding mitochondrial membrane integrity, and inhibiting cytochrome C release.…”

Section: Discussionmentioning

confidence: 99%

Neuregulin 1 Attenuates Neuronal Apoptosis Induced by Deep Hypothermic Circulatory Arrest Through ErbB4 Signaling in Rats

Wang

et al. 2015

Journal of Cardiovascular Pharmacology

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Mounting evidence suggests that neurological injury occurs after deep hypothermic circulatory arrest (DHCA), a protocol widely used in surgery for congenital heart diseases and aortic repair. Neuregulin 1 (NRG1), a neurotrophic factor highly expressed in the central nervous system, is crucial for neuronal survival. However, whether NRG1 is protective against apoptosis induced by DHCA is still unclear, as are the putative mechanisms involved. In this study, exogenous human NRG1 pretreatment (2.5 and 3.75 ng/kg, intracarotid injection) significantly inhibited neuronal apoptosis in DHCA-treated male rats, and notably, endogenous NRG1 expression was also increased. Bcl-2, as well as phosphorylated phosphatidylinositol-3-kinase, Akt, and cAMP-response element binding protein, were all increased, resulting in phosphorylation and subsequent activation of the ErbB4 receptor. Finally, expression of the apoptosis-related protein cleaved-caspase-3 was decreased, resulting in the inhibition of neuronal apoptosis induced by DHCA. Thus, our data indicate that NRG1 treatment inhibited DHCA-induced neuronal apoptosis by activating ErbB4 signaling, providing a potential therapeutic pathway for the prevention of neurological injury induced by DHCA.

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Section: Discussionmentioning

confidence: 99%

Neuregulin 1 Attenuates Neuronal Apoptosis Induced by Deep Hypothermic Circulatory Arrest Through ErbB4 Signaling in Rats

Wang

et al. 2015

Journal of Cardiovascular Pharmacology

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“…GSK-3 has been most extensively studied as a kinase for tau, although it is also involved in Aβ production 54. GSK-3 is a multifunctional serine/threonine kinase that is affected by both the phosphorylation and aggregation of tau.…”

Section: Alzheimer's Disease: Brain Insulin Resistancementioning

confidence: 99%

Metabolism-Centric Overview of the Pathogenesis of Alzheimer's Disease

2017

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Alzheimer's disease (AD) is a degenerative brain disease and the most common cause of dementia. AD is characterized by the extracellular amyloid beta (Aβ) plaques and intraneuronal deposits of neurofibrillary tangles (NFTs). Recently, as aging has become a familiar phenomenon around the world, patients with AD are increasing in number. Thus, many researchers are working toward finding effective therapeutics for AD focused on Aβ hypothesis, although there has been no success yet. In this review paper, we suggest that AD is a metabolic disease and that we should focus on metabolites that are affected by metabolic alterations to find effective therapeutics for AD. Aging is associated with not only AD but also obesity and type 2 diabetes (T2DM). AD, obesity, and T2DM share demographic profiles, risk factors, and clinical and biochemical features in common. Considering AD as a kind of metabolic disease, we suggest insulin, adiponectin, and antioxidants as mechanistic links among these diseases and targets for AD therapeutics. Patients with AD show reduced insulin signal transductions in the brain, and intranasal injection of insulin has been found to have an effect on AD treatment. In addition, adiponectin is decreased in the patients with obesity and T2DM. This reduction induces metabolic dysfunction both in the body and the brain, leading to AD pathogenesis. Oxidative stress is known to be induced by Aβ and NFTs, and we suggest that oxidative stress caused by metabolic alterations in the body induce brain metabolic alterations, resulting in AD.

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“…Regulatory subunits p85α of PI3K promote the nuclear translocation of XBP1s 35, 36, 37. cAMP response element-binding protein (CREB) is activated in AD models by PI3K/Akt, and its phosphorylation is neuroprotective 38, 39. CREB is also activated by ER stress, and it binds to the promoter of the IRE1α gene and regulates its expression 40 .…”

Section: Resultsmentioning

confidence: 99%

“…Its activation exhibits neuroprotection via the PI3K/Akt/CREB pathway in AD models 38, 39. CREB is also activated by ER stress: a chromatin immunoprecipitation assay indicated that CREB binds to the promoter region of IRE1α genes and regulates its expression 40 .…”

Section: Discussionmentioning

confidence: 99%

Tat-haFGF 14–154 Upregulates ADAM10 to Attenuate the Alzheimer Phenotype of APP/PS1 Mice through the PI3K-CREB-IRE1α/XBP1 Pathway

Meng

Cao

Lei

et al. 2017

Molecular Therapy - Nucleic Acids

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Acid fibroblast growth factor (aFGF) has shown neuroprotection in Alzheimer’s disease (AD) models in previous studies, yet its mechanism is still uncertain. Here we report that the efficacy of Tat-haFGF14–154 is markedly increased when loaded cationic liposomes for intranasal delivery are intranasally administered to APP/PS1 mice. Our results demonstrated that liposomal Tat-haFGF14–154 treatment significantly ameliorated behavioral deficits, relieved brain Aβ burden, and increased the expression and activity of disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in the brain. Tat-haFGF14–154 antagonized Aβ1–42-induced cell death and structural damage in rat primary neurons in an ADAM10-dependent manner, which, in turn, was promoted by the activation of XBP1 splicing and modulated by the PI3K-CREB pathway. Both knockdown of ADAM10 and inhibition of PI3K (LY294002) negated Tat-haFGF14–154 rescue. Thus, Tat-haFGF14–154 activates the IRE1α/XBP1 pathway of the unfolded protein response (UPR) against the endoplasmic reticulum (ER) stress induced by Aβ, and, subsequently, the nuclear translocation of spliced XBP1 (XBP1s) promotes transcription of ADAM10. These results highlight the important role of ADAM10 and its activation through the PI3K-CREB-IRE1α/XBP1 pathway as a key factor in the mechanism of neuroprotection for Tat-haFGF14–154.

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Illite improves memory impairment and reduces Aβ level in the Tg-APPswe/PS1dE9 mouse model of Alzheimer׳s disease through Akt/CREB and GSK-3β phosphorylation in the brain

Cited by 15 publications

References 45 publications

Neuregulin 1 Attenuates Neuronal Apoptosis Induced by Deep Hypothermic Circulatory Arrest Through ErbB4 Signaling in Rats

Neuregulin 1 Attenuates Neuronal Apoptosis Induced by Deep Hypothermic Circulatory Arrest Through ErbB4 Signaling in Rats

Metabolism-Centric Overview of the Pathogenesis of Alzheimer's Disease

Tat-haFGF 14–154 Upregulates ADAM10 to Attenuate the Alzheimer Phenotype of APP/PS1 Mice through the PI3K-CREB-IRE1α/XBP1 Pathway

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