ArticleFrontiers in aging neuroscience2022
Discovery of Novel Drug Candidates for Alzheimer's Disease by Molecular Network Modeling.
Article in Frontiers in aging neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
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- Multilayer Analysis of RNA Sequencing Data in Alzheimer's Disease to Unravel Molecular Mysteries.Advances in neurobiology · 2024Review
- New Biotinylated GHK and Related Copper(II) Complex: Antioxidant and Antiglycant Properties In Vitro against Neurodegenerative Disorders.Molecules (Basel, Switzerland) · 2023Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To identify the molecular mechanisms and novel therapeutic agents of late-onset Alzheimer's disease (AD), we performed integrative network analysis using multiple transcriptomic profiles of human brains. With the hypothesis that AD pathology involves the whole cerebrum, we first identified co-expressed modules across multiple cerebral regions of the aging human brain. Among them, two modules (M3 and M8) consisting of 1,429 protein-coding genes were significantly enriched with AD-correlated genes. Differential expression analysis of microarray, bulk RNA-sequencing (RNA-seq) data revealed the dysregulation of M3 and M8 across different cerebral regions in both normal aging and AD. The cell-type enrichment analysis and differential expression analysis at the single-cell resolution indicated the extensive neuronal vulnerability in AD pathogenesis. Transcriptomic-based drug screening from Connectivity Map proposed Gly-His-Lys acetate salt (GHK) as a potential drug candidate that could probably restore the dysregulated genes of the M3 and M8 network. Pretreatment with GHK showed a neuroprotective effect against amyloid-beta-induced injury in differentiated human neuron-like SH-SY5Y cells. Taken together, our findings uncover a dysregulated network disrupted across multiple cerebral regions in AD and propose pretreatment with GHK as a novel neuroprotective strategy against AD.
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