2. Academic Validation
  3. SNAP25 is a potential target for early stage Alzheimer's disease and Parkinson's disease

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

  • Eur J Med Res. 2023 Dec 6;28(1):570. doi: 10.1186/s40001-023-01360-8.
Qian Wang # 1,  Sijue Tao # 2,  Lei Xing 3,  Jiuyu Liu 3,  Cankun Xu 3,  Xinyi Xu 3,  Haohan Ding 3,  Qi Shen 4,  Xiaobo Yu 5,  Yingwei Zheng 6
Affiliations

Affiliations

  • 1 Department of Radiology, Xuzhou Central Hospital, Xuzhou, 221004, Jiangsu, China.
  • 2 Laboratory Animal Center, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
  • 3 Jiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
  • 4 Neurological Institute, Columbia University, NY Presbyterian Hospital, New York, NY, USA. [email protected].
  • 5 National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal University, Xi'an, 710062, Shanxi, China. [email protected].
  • 6 Jiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China. [email protected].
  • # Contributed equally.
PMID: 38053192 DOI: 10.1186/s40001-023-01360-8
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.

Keywords

Alzheimer’s disease; Bioinformatical analysis; Comorbidity mechanism; Olfactory system; Parkinson’s disease; SNAP25.

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