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Activation of apoptotic signaling by DAPK1 suppresses neural remodeling and functional recovery in stroke
Author(s) -
Hong Yonggeun,
Won Jinyoung,
Choi Jeonghyun,
Kim Joo-Heon
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09289
Subject(s) - stroke (engine) , autophagy , apoptosis , neuroprotection , medicine , downregulation and upregulation , ischemia , neuroscience , biology , biochemistry , gene , mechanical engineering , engineering
Death‐associated protein kinase 1 (DAPK1), a key player in multiple types of cell death, is activated in ischemic stroke. We examined whether suppression of DAPK1 contributes to neuronal regeneration and, thereby, improves functional outcomes. Animals were subjected to middle cerebral artery occlusion (MCAo) and were administered an oxazolone‐based DAPK1 inhibitor. Animals with ischemic stroke had neurological damage and altered behavioral outcomes. However, DAPK1 inhibitor treatment reduced the expansion of the ischemic infarct and improved functional recovery. Inhibition of DAPK1 attenuated the structural abnormalities of the cortical pyramidal neurons and progressively improved neurological deficits. Additionally, while the levels of anti‐apoptotic proteins were upregulated, those of pro‐apoptotic and autophagy‐related proteins were down‐regulated in the ischemic brain by DAPK1 inhibition. Likewise, brain infarct volume and neurological deficit scores were reduced in DAPK1 KO mice. Activation of DAPK1 was exclusively associated with brain injury. These findings suggest that modulation of apoptosis by DAPK1 suppression could be used to treat ischemic stroke. Support or Funding Information National Research Foundation (NRF‐2013R1A2A2A01067169, NRF‐2017R1D1A1B03029565) Korea, Creative Research Program (2016–2017) of Inje University, Korea.