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Abnormal upregulation of DAPK1 is observed in human patients with neurological diseases, such as Alzheimer\u2019s disease (AD) and epilepsy. Ablation of DAPK1 expression and suppression of DAPK1 activity attenuates neuropathology and behavior impairments. However, whether DAPK1 regulates gene expression in the brain, and whether its gene profile is implicated in neuronal disorders, remains elusive. To reveal the function and pathogenic role of DAPK1 in neurological diseases in the brain, differential transcriptional profiling was performed in the brains of DAPK1 knockout (DAPK1-KO) mice compared with those of wild-type (WT) mice by RNA sequencing. We showed significantly altered genes in the cerebral cortex, hippocampus, brain stem, and cerebellum of both male and female DAPK1-KO mice compared to those in WT mice, respectively. The genes are implicated in multiple neural-related pathways, including: AD, Parkinson\u2019s disease (PD), Huntington\u2019s disease (HD), neurodegeneration, glutamatergic synapse, and GABAergic synapse pathways. Moreover, our findings imply that the potassium voltage-gated channel subfamily A member 1 (Kcna1) may be involved in the modulation of DAPK1 in epilepsy. Our study provides insight into the pathological role of DAPK1 in the regulatory networks in the brain and new therapeutic strategies for the treatment of neurological diseases.<\/jats:p>","DOI":"10.3390\/ijms24076542","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T03:31:38Z","timestamp":1680233498000},"page":"6542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Ablation of Death-Associated Protein Kinase 1 Changes the Transcriptomic Profile and Alters Neural-Related Pathways in the Brain"],"prefix":"10.3390","volume":"24","author":[{"given":"Ruomeng","family":"Li","sequence":"first","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, Institute of Basic Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Zhi","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China"},{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guihua","family":"Lan","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, Institute of Basic Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaotong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China"},{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuzhi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, Institute of Basic Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Hu","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, Institute of Basic Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Wang","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, Institute of Basic Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, Institute of Basic Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5968-1478","authenticated-orcid":false,"given":"Tae Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, Institute of Basic Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shitao","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China"},{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongmei","family":"Chen","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, Institute of Basic Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kim, N., Chen, D., Zhou, X.Z., and Lee, T.H. 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