scholarly journals Suppression of Alzheimer's disease‑related phenotypes by the heat shock protein 70 inducer, geranylgeranylacetone, in APP/PS1 transgenic mice via the ERK/p38 MAPK signaling pathway

2017 ◽  
Author(s):  
Yuan Sun ◽  
Jiang‑Rong Zhang ◽  
Shuyan Chen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heat Shock ◽  
Transgenic Mice ◽  
Heat Shock Protein ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Heat Shock Protein 70 ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway

scholarly journals SkQ1 Suppresses the p38 MAPK Signaling Pathway Involved in Alzheimer’s Disease-Like Pathology in OXYS Rats

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 676
Author(s):  
Natalia A. Muraleva ◽  
Natalia A. Stefanova ◽  
Nataliya G. Kolosova
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Oxys Rats ◽  
Mitogen Activated Protein Kinase ◽  
Immunofluorescent Staining ◽  
Αb Crystallin

Alzheimer’s disease (AD) is the most common type of dementia and is currently incurable, and mitogen-activated protein kinase (MAPK) p38 is implicated in the pathogenesis of AD. p38 MAPK inhibition is considered a promising strategy against AD, but there are no safe inhibitors capable of penetrating the blood–brain barrier. Earlier, we have shown that mitochondria-targeted antioxidant plastoquinonyl-decyltriphenylphosphonium (SkQ1) at nanomolar concentrations can prevent, slow down, or partially alleviate AD-like pathology in accelerated-senescence OXYS rats. Here we confirmed that dietary supplementation with SkQ1 during active progression of AD-like pathology in OXYS rats (aged 12–18 months) suppresses AD-like pathology progression, and for the first time, we showed that its effects are associated with suppression of p38 MAPK signaling pathway (MAPKsp) activity. Transcriptome analysis, western blotting, and immunofluorescent staining revealed that SkQ1 suppresses p38 MAPKsp activity in the hippocampus at the level of expression of genes involved in the p38 MAPKsp and reduces the phosphorylation of intermediate kinases (p38 MAPK and MK2) and a downstream protein (αB-crystallin). Thus, the anti-AD effects of SkQ1 are associated with improvement in the functioning of relevant signaling pathways and intracellular processes, thus making it a promising therapeutic agent for human AD.

scholarly journals MKP-1 reduces Aβ generation and alleviates cognitive impairments in Alzheimer’s disease models

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Yehong Du ◽  
Yexiang Du ◽  
Yun Zhang ◽  
Zhilin Huang ◽  
Min Fu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Amyloid Β ◽  
Gene Promoter ◽  
Long Term Potentiation ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase

AbstractMitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is an essential negative regulator of MAPKs by dephosphorylating MAPKs at both tyrosine and threonine residues. Dysregulation of the MAPK signaling pathway has been associated with Alzheimer’s disease (AD). However, the role of MKP-1 in AD pathogenesis remains elusive. Here, we report that MKP-1 levels were decreased in the brain tissues of patients with AD and an AD mouse model. The reduction in MKP-1 gene expression appeared to be a result of transcriptional inhibition via transcription factor specificity protein 1 (Sp1) cis-acting binding elements in the MKP-1 gene promoter. Amyloid-β (Aβ)-induced Sp1 activation decreased MKP-1 expression. However, upregulation of MKP-1 inhibited the expression of both Aβ precursor protein (APP) and β-site APP-cleaving enzyme 1 by inactivating the extracellular signal-regulated kinase 1/2 (ERK)/MAPK signaling pathway. Furthermore, upregulation of MKP-1 reduced Aβ production and plaque formation and improved hippocampal long-term potentiation (LTP) and cognitive deficits in APP/PS1 transgenic mice. Our results demonstrate that MKP-1 impairment facilitates the pathogenesis of AD, whereas upregulation of MKP-1 plays a neuroprotective role to reduce Alzheimer-related phenotypes. Thus, this study suggests that MKP-1 is a novel molecule for AD treatment.

scholarly journals Heat shock protein 90α couples with the MAPK-signaling pathway to determine meiotic maturation of porcine oocytes1

2018 ◽  
Vol 96 (8) ◽  
pp. 3358-3369 ◽  
Author(s):  
Yun-Hua Liu ◽  
Xiao-Man Liu ◽  
Pei-Chao Wang ◽  
Xiao-Xia Yu ◽  
Jia-Kun Miao ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Meiotic Maturation

scholarly journals Downregulation of TREM2 Expression Exacerbates Neuroinflammatory Responses Through TLR4-Mediated MAPK Signaling Pathway in a Transgenic Mouse Model of Alzheimer’s Disease

2021 ◽  
Author(s):  
John Bosco Ruganzu ◽  
Xiaoqian Peng ◽  
Yingying He ◽  
Xiangyuan Wu ◽  
Quzhao Zheng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mechanistic Study ◽  
Model Of Alzheimer’S Disease ◽  
Bv2 Cells ◽  
The Brain

Abstract Activation of glial cells and neuroinflammation play an important role in the onset and development of Alzheimer’s disease (AD). Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-specific receptor in the brain that is involved in regulating neuroinflammation. However, the precise effects of TREM2 on neuroinflammatory responses and its underlying molecular mechanisms in AD have not been studied in detail. Here, we employed a lentiviral-mediated strategy to downregulation of TREM2 expression on microglia in the brain of APPswe/PS1dE9 (APP/PS1) transgenic mice and BV2 cells. Our results showed that TREM2 downregulation significantly aggravated AD-related neuropathology including Aβ accumulation, peri-plaque microgliosis and astrocytosis, as well as neuronal and synapse-associated proteins loss, which was accompanied by a decline in cognitive ability. The further mechanistic study revealed that downregulation of TREM2 expression initiated neuroinflammatory responses through toll-like receptor 4 (TLR4)-mediated mitogen-activated protein kinase (MAPK) signaling pathway and subsequent stimulating the production of pro-inflammatory cytokines in vivo and in vitro. Moreover, blockade of p38, JNK, and ERK1/2 inhibited the release of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) induced by Aβ1−42 in TREM2-knocked down BV2 cells. Taken together, these findings indicated that TREM2 might be a potential therapeutic target for AD and other neuroinflammation related diseases.

scholarly journals Suppression of Alzheimer's Disease-Related Phenotypes by Expression of Heat Shock Protein 70 in Mice

2011 ◽  
Vol 31 (14) ◽  
pp. 5225-5234 ◽  
Author(s):  
T. Hoshino ◽  
N. Murao ◽  
T. Namba ◽  
M. Takehara ◽  
H. Adachi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70

scholarly journals Heat Shock Protein 70 in Alzheimer’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Rui-Chun Lu ◽  
Meng-Shan Tan ◽  
Hao Wang ◽  
An-Mu Xie ◽  
Jin-Tai Yu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Protein Misfolding ◽  
Cell Loss ◽  
Protein Misfolding Disorder

Alzheimer’s disease (AD) is the most common neurodegenerative disease that caused dementia which has no effective treatment. Growing evidence has demonstrated that AD is a “protein misfolding disorder” that exhibits common features of misfolded, aggregation-prone proteins and selective cell loss in the mature nervous system. Heat shock protein 70 (HSP70) attracts extensive attention worldwide, because it plays a crucial role in preventing protein misfolding and inhibiting aggregation and represents a class of proteins potentially involved in AD pathogenesis. Numerous studies have indicated that HSP70 could suppress the progression of AD within vitroandin vivoexperiments. Thus, targeting HSP70 and the related compounds might represent a promising strategy for the treatment of AD.

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