PMID- 35202858
OWN - NLM
STAT- MEDLINE
DCOM- 20220429
LR  - 20220531
IS  - 1872-9649 (Electronic)
IS  - 1568-1637 (Linking)
VI  - 76
DP  - 2022 Apr
TI  - Neurodegenerative effect of DAPK1 after cerebral hypoxia-ischemia is associated 
      with its post-transcriptional and signal transduction regulations: A systematic 
      review and meta-analysis.
PG  - 101593
LID - S1568-1637(22)00035-6 [pii]
LID - 10.1016/j.arr.2022.101593 [doi]
AB  - Cerebral hypoxia-ischemia (CHI) causes brain aging, neurological disorders, 
      cognitive decline, motor function impairment, and mortality. Inhibiting 
      death-associated protein kinase 1 (DAPK1) has shown therapeutic potential against 
      CHI, but several reports contradict its protective function, mechanism of 
      activation, and signal transduction. Here, we systematically reviewed the role 
      and the activation mechanism of DAPK1, and quantitatively assess the efficacy of 
      DAPK1 inhibition (DI) methods in neuroprotection, following a CHI in animal 
      models. Embase and PubMed were searched for relevant studies. Overall, 13 studies 
      met the inclusion criteria, and the SYRCLE Risk of bias tool (RoB) tool was used 
      to assess RoB. StataSE 16 was used for meta-analysis and network meta-analysis 
      (NMA). Standardized mean differences (SMD) with 95% confidence intervals (CI) 
      were calculated to estimate the effect size. DI was associated with the reduction 
      of brain infarct volume (BIV) [SMD = -1.70, 95% CI (-2.10, -1.30); p = 0.00], 
      neurological score (N.S.), neuronal degeneration, with no change in the level of 
      in cell death [SMD = -0.83, 95% CI (-2.00, 0.35); p = 0.17], indicating the 
      protective role of DI against CHI. No differences were found in DAPK1 mRNA and 
      protein levels [SMD = 0.50, 95% CI (-0.05, 1.04); p = 0.07] single-study driven; 
      upregulated after exclusion (p = 0.01, I(2) = 36.43), whereas phospho-DAPK1 
      [SMD = -2.22, 95% CI (-3.69, -0.75); p = 0.00] was downregulated and 
      phosphorylated myosin light chain [SMD = 3.37, 95% CI (2.51, 4.96); p = 0.00] was 
      upregulated between CHI and sham groups. Furthermore, we performed NMA to 
      understand the molecular level at which DI offers maximum protection against BIV. 
      Post-transcriptional inhibition (PTI; SUCRA, 82.6%) and gene knockout showed best 
      (KO; SUCRA, 81.3%), signal transduction inhibition (STI; SUCRA, 49.5%) offered 
      3(rd) best, while catalytic activity inhibition (CAI; SUCRA, 0.3%) exhibited the 
      lowest reduction in BIV against CHI. The results demonstrate that DI has a 
      neuroprotective effect against CHI and DAPK1 might be regulated at the 
      post-transcriptional and post-translational levels after CHI. Inhibiting DAPK1 at 
      the post-transcriptional level and blocking multiple signal transduction pathways 
      of DAPK1 could lead to better functional recovery against CHI. AVAILABILITY OF 
      DATA AND MATERIALS: The datasets used and/or analyzed during the current study 
      are available from the corresponding author on reasonable request.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Khan, Zeeshan Ahmad
AU  - Khan ZA
AD  - Department of Physical Therapy, College of Healthcare Medical Science & 
      Engineering, Gimhae 50834, South Korea; Research Center for Aged-Life redesign, 
      Inje University, Gimhae 50834, South Korea; Biohealth Products Research Center 
      (BPRC), Inje University, Gimhae 50834, South Korea. Electronic address: 
      acezeeshan@live.com.
FAU - Sumsuzzman, Dewan Md
AU  - Sumsuzzman DM
AD  - Department of Physical Therapy, College of Healthcare Medical Science & 
      Engineering, Gimhae 50834, South Korea; Research Center for Aged-Life redesign, 
      Inje University, Gimhae 50834, South Korea; Biohealth Products Research Center 
      (BPRC), Inje University, Gimhae 50834, South Korea. Electronic address: 
      dewanpavelpharm@google.com.
FAU - Choi, Jeonghyun
AU  - Choi J
AD  - Department of Physical Therapy, College of Healthcare Medical Science & 
      Engineering, Gimhae 50834, South Korea; Research Center for Aged-Life redesign, 
      Inje University, Gimhae 50834, South Korea; Biohealth Products Research Center 
      (BPRC), Inje University, Gimhae 50834, South Korea. Electronic address: 
      yiopiop0011@nate.com.
FAU - Hong, Yonggeun
AU  - Hong Y
AD  - Department of Physical Therapy, College of Healthcare Medical Science & 
      Engineering, Gimhae 50834, South Korea; Research Center for Aged-Life redesign, 
      Inje University, Gimhae 50834, South Korea; Biohealth Products Research Center 
      (BPRC), Inje University, Gimhae 50834, South Korea; Department of Rehabilitation 
      Science, Graduate School of Inje University, Gimhae 50834, South Korea. 
      Electronic address: yonghong@inje.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PT  - Systematic Review
DEP - 20220222
PL  - England
TA  - Ageing Res Rev
JT  - Ageing research reviews
JID - 101128963
RN  - EC 2.7.11.1 (DAPK1 protein, human)
RN  - EC 2.7.11.1 (Death-Associated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cell Death
MH  - *Death-Associated Protein Kinases/genetics/metabolism
MH  - Humans
MH  - *Hypoxia-Ischemia, Brain/genetics
MH  - Network Meta-Analysis
MH  - *Neurodegenerative Diseases/genetics
MH  - RNA Processing, Post-Transcriptional
MH  - *Signal Transduction
OTO - NOTNLM
OT  - Cerebral hypoxia-ischemia
OT  - Death-associated protein kinase 1
OT  - Meta-analysis
OT  - Systematic review
EDAT- 2022/02/25 06:00
MHDA- 2022/04/30 06:00
CRDT- 2022/02/24 20:11
PHST- 2021/04/16 00:00 [received]
PHST- 2022/01/10 00:00 [revised]
PHST- 2022/02/18 00:00 [accepted]
PHST- 2022/02/25 06:00 [pubmed]
PHST- 2022/04/30 06:00 [medline]
PHST- 2022/02/24 20:11 [entrez]
AID - S1568-1637(22)00035-6 [pii]
AID - 10.1016/j.arr.2022.101593 [doi]
PST - ppublish
SO  - Ageing Res Rev. 2022 Apr;76:101593. doi: 10.1016/j.arr.2022.101593. Epub 2022 Feb 
      22.