Upregulation of the lncRNA MEG3 improves cognitive impairment, alleviates neuronal damage, and inhibits activation of astrocytes in hippocampus tissues in Alzheimer's disease through inactivating the PI3K/Akt signaling pathway

Alzheimer’s disease (AD), a leading cause of dementia, remained incurable, despite many advances in our knowledge about AD pathogenesis, underlying mechanisms are poorly understood. Transcriptome analysis showed efficiency in exploring these mechanisms; however, data are generated at a higher pace than interpreted and are almost inconsistent. Therefore we performed this meta-analysis to extract new knowledge from existing data and find the mechanisms involved in AD. Five temporal cortex transcriptomics datasets from 187 AD patients and 167 healthy controls were analyzed. Our analysis showed that the PI3K-Akt signaling pathway is significantly impaired in AD brains and was common among all datasets. Moreover, miRs targeting genes involved in the PI3K-Akt signaling pathway were identified. In conclusion, our results highlight the impaired PI3K-Akt signaling pathway in AD and suggested related miRs as the potential targets for early treatment and diagnosis of AD.

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Ganoderma lucidum Triterpenoids (GLTs) Reduce Neuronal Apoptosis via Inhibition of ROCK Signal Pathway in APP/PS1 Transgenic Alzheimer’s Disease Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/9894037 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Nanhui Yu ◽

Yongpan Huang ◽

Yu Jiang ◽

Lianhong Zou ◽

Xiehong Liu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Signaling Pathway ◽

Ganoderma Lucidum ◽

Hippocampal Neurons ◽

Caspase 3 ◽

Neuronal Damage ◽

Tunel Staining ◽

Ganoderma Lucidum Triterpenoids

Alzheimer’s disease (AD) is the most common cause of dementia among senior citizen. Ganoderma lucidum triterpenoids (GLTs) have nutritional health benefits and has been shown to promote health and longevity, but a protective effect of GLTs on AD damage has not yet been reported. The objective of this research was to elucidate the phylactic effect of GLTs on AD model mice and cells and to explore its underlying mechanisms. Morris water maze (MWM) test was conducted to detect changes in the cognitive function of mice. Hematoxylin-eosin (HE) staining was applied to observe pathological changes in the hippocampus. Silver nitrate staining was applied to observe the hippocampal neuronal tangles (NFTs). Apoptosis of the hippocampal neurons in mouse brain tissue was determined by TUNEL staining. The expression levels of apoptosis-related protein Bcl2, Bax, and caspase 3/cleaved caspase 3; antioxidative protein Nrf2, NQO1, and HO1; and ROCK signaling pathway-associated proteins ROCK2 and ROCK1 were measured by western blot. In vivo experiments show that 5-month-old APP/PS1 mice appeared to have impaired acquisition of spatial learning and GLTs could reduce cognitive impairment in AD mice. Compared to normal mice, the hippocampus of APP/PS1 mouse’s brains was severely damaged, while GLTs could alleviate this symptom by inhibiting apoptosis, relieving oxidative damage, and inactivating the ROCK signaling pathway. In in vitro cell experiments, Aβ25-35 was applied to induce hippocampal neurons into AD model cells. GLTs promoted cell proliferation, facilitated superoxide dismutase (SOD) expression, and inhibited malondialdehyde (MDA) and lactic dehydrogenase (LDH) expression of neurons. Our study highlights that GLTs improve cognitive impairment, alleviate neuronal damage, and inhibit apoptosis in the hippocampus tissues and cells in AD through inhibiting the ROCK signaling pathway.

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Identifying mechanisms of Epimedii Folium against Alzheimer’s disease via a network pharmacology approach Epimedii Folium treats Alzheimer’s disease via PI3K-AKT

European Journal of Inflammation ◽

10.1177/20587392211041435 ◽

2021 ◽

Vol 19 ◽

pp. 205873922110414

Author(s):

Yan Zhao ◽

Guangmei Liu ◽

Yang Yang ◽

Ling Chen ◽

Ying Shang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Signaling Pathway ◽

Target Genes ◽

Kegg Pathway ◽

Target Therapy ◽

Akt Signaling ◽

Network Pharmacology ◽

Akt Signaling Pathway ◽

Pathway Gene

To elucidate the mechanism of the multi-target action of Epimedii Folium on Alzheimer’s disease, this study focuses on the analysis of network pharmacology. Based on a bioinformatics approach, this study obtained the effective components of Epimedium through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, predicted the compound targets through the Pharmapper and Swiss target prediction database and then through Gene Expression Omnibus Datasets and Therapeutic Target Database. We collected and analysed of heral and disease targets, constructed the network. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene Ontology enrichment, then the key targets and pathways of Epimedii Folium to cope with Alzheimer’s disease have been identified. Twenty-three bioactive components and 477 potential target genes of Epimedii Folium were identified. A total of 1612 target diseases were identified. Through network module analysis, 30 hub target genes were identified. Through enrichment analysis of the KEGG pathway, hub target genes were largely enriched in the PI3K-AKT signaling pathway. Through the analysis of network pharmacology, it was found that Epimedii Folium might play the role of multi-compound and multi-target therapy through the PI3K-AKT signaling pathway. These findings provide helpful directions for future clinical studies.

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PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer’s Disease and Parkinson’s Disease

Frontiers in Pharmacology ◽

10.3389/fphar.2021.648636 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hui-Zhi Long ◽

Yan Cheng ◽

Zi-Wei Zhou ◽

Hong-Yu Luo ◽

Dan-Dan Wen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Natural Products ◽

Signaling Pathway ◽

Glycogen Synthase ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Gsk 3Β

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are two typical neurodegenerative diseases that increased with aging. With the emergence of aging population, the health problem and economic burden caused by the two diseases also increase. Phosphatidylinositol 3-kinases/protein kinase B (PI3K/AKT) signaling pathway regulates signal transduction and biological processes such as cell proliferation, apoptosis and metabolism. According to reports, it regulates neurotoxicity and mediates the survival of neurons through different substrates such as forkhead box protein Os (FoxOs), glycogen synthase kinase-3β (GSK-3β), and caspase-9. Accumulating evidences indicate that some natural products can play a neuroprotective role by activating PI3K/AKT pathway, providing an effective resource for the discovery of potential therapeutic drugs. This article reviews the relationship between AKT signaling pathway and AD and PD, and discusses the potential natural products based on the PI3K/AKT signaling pathway to treat two diseases in recent years, hoping to provide guidance and reference for this field. Further development of Chinese herbal medicine is needed to treat these two diseases.

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