Emerging role of PARP-1 and PARthanatos in ischemic stroke.
Shuiqiao LiuWeibo LuoYingfei WangPublished in: Journal of neurochemistry (2021)
Cell death is a key feature of neurological diseases, including stroke and neurodegenerative disorders. Studies in a variety of ischemic/hypoxic mouse models demonstrate that poly(ADP-ribose) polymerase 1 (PARP-1)-dependent cell death, also named PARthanatos, plays a pivotal role in ischemic neuronal cell death and disease progress. PARthanatos has its unique triggers, processors, and executors that convey a highly orchestrated and programmed signaling cascade. In addition to its role in gene transcription, DNA damage repair, and energy homeostasis through PARylation of its various targets, PARP-1 activation in neuron and glia attributes to brain damage following ischemia/reperfusion. Pharmacological inhibition or genetic deletion of PARP-1 reduces infarct volume, eliminates inflammation, and improves recovery of neurological functions in stroke. Here, we reviewed the role of PARP-1 and PARthanatos in stroke and their therapeutic potential.
Keyphrases
- dna damage
- cell death
- cerebral ischemia
- dna repair
- oxidative stress
- atrial fibrillation
- subarachnoid hemorrhage
- blood brain barrier
- brain injury
- cell cycle arrest
- ischemia reperfusion injury
- copy number
- transcription factor
- signaling pathway
- acute myocardial infarction
- gene expression
- dna methylation
- acute coronary syndrome
- coronary artery disease