J Clin Neurol.  2015 Oct;11(4):297-304. 10.3988/jcn.2015.11.4.297.

The Role of the PI3K Pathway in the Regeneration of the Damaged Brain by Neural Stem Cells after Cerebral Infarction

Affiliations
  • 1Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. ksh213@hanyang.ac.kr
  • 2Department of Neurology, Hanyang University College of Medicine, Seoul, Korea.

Abstract

Neurologic deficits resulting from stroke remain largely intractable, which has prompted thousands of studies aimed at developing methods for treating these neurologic sequelae. Endogenous neurogenesis is also known to occur after brain damage, including that due to cerebral infarction. Focusing on this process may provide a solution for treating neurologic deficits caused by cerebral infarction. The phosphatidylinositol-3-kinase (PI3K) pathway is known to play important roles in cell survival, and many studies have focused on use of the PI3K pathway to treat brain injury after stroke. Furthermore, since the PI3K pathway may also play key roles in the physiology of neural stem cells (NSCs), eliciting the appropriate activation of the PI3K pathway in NSCs may help to improve the sequelae of cerebral infarction. This review describes the PI3K pathway, its roles in the brain and NSCs after cerebral infarction, and the therapeutic possibility of activating the pathway to improve neurologic deficits after cerebral infarction.

Keyword

neural stem cells; stroke; phosphatidylinositol-3-kinases; regeneration

MeSH Terms

Brain Injuries
Brain*
Cell Survival
Cerebral Infarction*
Neural Stem Cells*
Neurogenesis
Neurologic Manifestations
Physiology
Regeneration*
Stroke

Figure

  • Fig. 1 Role of the phosphatidylinositol-3-kinase (PI3K) pathway in cells. Akt: protein kinase B, BAD: Bcl-2-associated death promoter, FOXO1: forkhead box protein O1, GSK3β: glycogen synthase kinase 3β, MDM2: mouse double minute 2 homolog, mTOR: mammalian target of rapamycin, NF-kB: nuclear factor kappa-light-chain enhancer of activated B cells, PKC: protein kinase C, Ptdlns: phosphatidylinositol, PTEN: phosphatase and tensin homolog, RAC1: Ras-related C3 botulinum toxin substrate 1, SGK: serine/threonine-protein kinase, S6K: ribosomal protein S6 kinase.

  • Fig. 2 Alteration of the PI3K pathway after ischemia and reperfusion. Cas-3: caspase-3, Cyto C: cytochrome C, JNK: c-Jun N-terminal kinases.

  • Fig. 3 Molecular events in the PI3K pathway. CXCR4: C-X-C chemokine receptor type 4, EGFR: epidermal growth factor receptor, ERK: extracellular-signal-regulated kinase, FGFR: fibroblast growth factor receptor, Fkhr: forkhead transcription factor Foxo1, IR: insulin receptor, NGFR: nerve growth factor receptor, PDGFR: platelet-derived growth factor receptor, VEGFR: vascular endothelial growth factor receptor, XIAP: X-linked inhibitor of apoptosis protein.


Cited by  2 articles

The role of PI3K/AKT pathway and its therapeutic possibility in Alzheimer's disease
Hyun-Jung Yu, Seong-Ho Koh
Hanyang Med Rev. 2017;37(1):18-24.    doi: 10.7599/hmr.2017.37.1.18.

Postischemic Inflammation in Acute Stroke
Simone Vidale, Arturo Consoli, Marco Arnaboldi, Domenico Consoli
J Clin Neurol. 2017;13(1):1-9.    doi: 10.3988/jcn.2017.13.1.1.


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