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Multi-omics Analysis Revealed the Role of CCT2 in the Induction of Autophagy in Alzheimer's Disease

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Journal Front Genet
Date 2023 Jan 27
PMID 36704351
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Abstract

() is essential in various neurodegenerative diseases, albeit its role in the pathogenesis of Alzheimer's disease (AD) remains elusive. This study aimed to evaluate the role of in Alzheimer's disease. First, bioinformatics database analysis revealed that was significantly downregulated in patients with Alzheimer's disease and associated with autophagic clearance of β-amyloid. The 789 differentially expressed genes overlapped in AD-group and -low/high group, and the -high-associated genes screened by Pearson coefficients were enriched in protein folding, autophagy, and messenger RNA stability regulation pathways. These results suggest that is significantly and positively associated with multiple pathways linked to autophagy and negatively associated with neuronal death. The logistic prediction model with 13 key genes, such as , screened in this study better predicts Alzheimer's disease occurrence (AUC = 0.9671) and is a favorable candidate for predicting potential biological targets of Alzheimer's disease. Additionally, this study predicts reciprocal micro RNAs and small molecule drugs for hub genes. Our findings suggest that low expression may be responsible for the autophagy suppression in Alzheimer's disease, providing an accurate explanation for its pathogenesis and new targets and small molecule inhibitors for its treatment.

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