PMID- 26347605
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150908
LR  - 20201001
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 9
DP  - 2015
TI  - Tissue-type plasminogen activator is a neuroprotectant in the central nervous 
      system.
PG  - 304
LID - 10.3389/fncel.2015.00304 [doi]
LID - 304
AB  - Tissue-type plasminogen activator (tPA) is a serine proteinase found not only in 
      the intravascular space but also in a well-defined sub-set of neurons in the 
      brain. tPA is rapidly released from neurons after either exposure to hypoxia or 
      hypoglycemia in vitro, or the induction of cerebral ischemia in vivo. It has been 
      proposed that tPA has a neurotoxic effect in the ischemic brain. However, recent 
      evidence indicate that once released into the synaptic cleft tPA activates 
      specific cell signaling pathways that promote the detection and adaptation to 
      metabolic stress. More specifically, the non-proteolytic interaction of tPA with 
      N-methyl-D-aspartate receptors (NMDARs) and a member of the low-density 
      lipoprotein receptor (LDLR) family in dendritic spines activates the mammalian 
      target of rapamycin (mTOR) pathway that adapts cellular processes to the 
      availability of energy and metabolic resources. TPA-induced mTOR activation in 
      neurons leads to hypoxia-inducible factor 1alpha (HIF-1alpha) accumulation, 
      HIF-1alpha-induced expression and membrane recruitment of the neuronal transporter of 
      glucose GLUT3, and GLUT3-mediated uptake of glucose. These and other data 
      discussed in this Review suggest that the postulated neurotoxic effect of tPA 
      needs to be reconsidered and instead indicate the emergence of a new paradigm: 
      that tPA is an endogenous neuroprotectant in the central nervous system (CNS).
FAU - Yepes, Manuel
AU  - Yepes M
AD  - Department of Neurology and Center for Neurodegenerative Disease, Emory 
      University School of Medicine and Veterans Affairs Medical Center Atlanta, GA, 
      USA.
LA  - eng
GR  - R01 NS079331/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20150817
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC4538299
OTO - NOTNLM
OT  - cerebral ischemia
OT  - excitotoxicity
OT  - middle cerebral artery occlusion (MCAo)
OT  - neuroprotection
OT  - neurovascular unit (NVU)
OT  - plasminogen
OT  - tissue-type plasminogen activator (tPA)
EDAT- 2015/09/09 06:00
MHDA- 2015/09/09 06:01
PMCR- 2015/01/01
CRDT- 2015/09/09 06:00
PHST- 2015/04/29 00:00 [received]
PHST- 2015/07/27 00:00 [accepted]
PHST- 2015/09/09 06:00 [entrez]
PHST- 2015/09/09 06:00 [pubmed]
PHST- 2015/09/09 06:01 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2015.00304 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2015 Aug 17;9:304. doi: 10.3389/fncel.2015.00304. 
      eCollection 2015.