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Published in: European Journal of Medical Research 1/2023

Open Access 01-12-2023 | Alzheimer's Disease | Research

SNAP25 is a potential target for early stage Alzheimer’s disease and Parkinson’s disease

Authors: Qian Wang, Sijue Tao, Lei Xing, Jiuyu Liu, Cankun Xu, Xinyi Xu, Haohan Ding, Qi Shen, Xiaobo Yu, Yingwei Zheng

Published in: European Journal of Medical Research | Issue 1/2023

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Abstract

Background

Alzheimer’s disease (AD) and Parkinson’s disease (PD), two common irreversible neurodegenerative diseases, share similar early stage syndromes, such as olfaction dysfunction. Yet, the potential comorbidity mechanism of AD and PD was not fully elucidated.

Methods

The gene expression profiles of GSE5281 and GSE8397 were downloaded from the Gene Expression Omnibus (GEO) database. We utilized a series of bioinformatics analyses to screen the overlapped differentially expressed genes (DEGs). The hub genes were further identified by the plugin CytoHubba of Cytoscape and validated in the hippocampus (HIP) samples of APP/PS-1 transgenic mice and the substantial nigra (SN) samples of A53T transgenic mice by real-time quantitative polymerase chain reaction (RT-qPCR). Meanwhile, the expression of the target genes in the olfactory epithelium/bulb was detected by RT-qPCR. Finally, molecular docking was used to screen potential compounds for the target gene.

Results

One hundred seventy-four overlapped DEGs were identified in AD and PD. Five of the top ten enrichment pathways mainly focused on the synapse. Five hub genes were identified and further validated. As a common factor in AD and PD, the changes of synaptosomal-associated protein 25 (SNAP25) mRNA in olfactory epithelium/bulb were significantly decreased and had a strong association with those in the HIP and SN samples. Pazopanib was the optimal compound targeting SNAP25, with a binding energy of − 9.2 kcal/mol.

Conclusions

Our results provided a theoretical basis for understanding the comorbidity mechanism of AD and PD and highlighted that SNAP25 in the olfactory epithelium may serve as a potential target for early detection and intervention in both AD and PD.
Appendix
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Metadata
Title
SNAP25 is a potential target for early stage Alzheimer’s disease and Parkinson’s disease
Authors
Qian Wang
Sijue Tao
Lei Xing
Jiuyu Liu
Cankun Xu
Xinyi Xu
Haohan Ding
Qi Shen
Xiaobo Yu
Yingwei Zheng
Publication date
01-12-2023
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-023-01360-8

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