{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:19:05Z","timestamp":1790270345370,"version":"4.1.0"},"reference-count":60,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,1,17]]},"abstract":"<jats:p>Background: Alzheimer\u2019s disease (AD) is the most common form of neurodegenerative dementia among the elderly. Excitotoxicity has been implicated as playing a dominant role in AD, especially related to the hyperactivation of excitatory neurons. Death-associated protein kinase 1 (DAPK1) is a calcium\/calmodulin-dependent kinase and involved in the pathogenesis of AD, but the roles and mechanisms of DAPK1 in excitotoxicity in AD are still uncertain. Objective: We mainly explored the underlying mechanisms of DAPK1 involved in the excitotoxicity of AD and its clinical relevance. Methods: Differentiated SH-SY5Y human neuroblastoma cells, PS1 V97\u200aL transgenic mice, and human plasma samples were used. Protein expression was assayed by immunoblotting, and intracellular calcium and neuronal damage were analyzed by flow cytometry. Plasma DAPK1 was measured by ELISA. Results: We found that DAPK1 was activated after amyloid-\u03b2 oligomers (A\u03b2Os) exposure in differentiated SH-SY5Y cells. Besides, we found the phosphorylation of GluN2B subunit at Ser1303 was increased, which contributing to excitotoxicity and Ca2+ overload in SH-SY5Y cells. Inhibiting DAPK1 activity, knockdown of DAPK1 expression, and antagonizing GluN2B subunits could effectively prevent A\u03b2Os-induced activation of GluN2B subunit, Ca2+ overload, and neuronal apoptosis. Additionally, we found that DAPK1 was elevated in the brain of AD transgenic mouse and in the plasma of AD patients. Conclusion: Our finding will help to understand the mechanism of DAPK1 in the excitotoxicity in AD and provide a reference for the diagnosis and therapy of AD.<\/jats:p>","DOI":"10.3233\/jad-220747","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T10:10:09Z","timestamp":1670580609000},"page":"877-893","source":"Crossref","is-referenced-by-count":20,"title":["NMDA Receptor GluN2B Subunit Is Involved in Excitotoxicity Mediated by Death-Associated Protein Kinase 1 in Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"91","author":[{"given":"Ling-Zhi","family":"Xu","sequence":"first","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, P.R. China"},{"name":"Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, P.R. China"},{"name":"Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, P.R. China"},{"name":"Center of Alzheimer\u2019s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, P.R. China"},{"name":"Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing-Qiu","family":"Li","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, P.R. China"},{"name":"Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, P.R. China"},{"name":"Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, P.R. China"},{"name":"Center of Alzheimer\u2019s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, P.R. China"},{"name":"Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, P.R. China"},{"name":"Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, P.R. China"},{"name":"Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, P.R. China"},{"name":"Center of Alzheimer\u2019s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, P.R. China"},{"name":"Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, P.R. China"},{"name":"Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, P.R. China"},{"name":"Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, P.R. China"},{"name":"Center of Alzheimer\u2019s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, P.R. China"},{"name":"Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Qin","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, P.R. China"},{"name":"Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, P.R. China"},{"name":"Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, P.R. China"},{"name":"Center of Alzheimer\u2019s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, P.R. China"},{"name":"Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, P.R. China"},{"name":"Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, P.R. 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