Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human aquaporin-1 (hAQP1) is a water channel found in many tissues and potentially involved in several human pathologies. Selective inhibitors of hAQP1 are discussed as novel treatment opportunities for glaucoma, brain edema, inflammatory pain, and certain types of cancer. However, only very few potent and chemically attractive blockers have been reported to date. In this study we present three novel hAQP1 blockers that have been identified by virtual screening and inhibit water flux through hAQP1 in Xenopus laevis oocyte swelling assays at low micromolar concentrations. The newly discovered compounds display no chemical similarity to hitherto known hAQP1 blockers and bind at the extracellular entrance of the channel, close to the ar/R selectivity filter. Furthermore, mutagenesis studies showed that Lys36, which is not conserved among the hAQP family, is crucially involved in binding and renders the discovered compounds suitable as leads for the development of selective hAQP1 inhibitors.
ACS Chem Biol 2013 Jan 18
PMID:Discovery of novel human aquaporin-1 blockers. 2311 56

We investigated the effect of the VEGF-mimetic peptide, QK, on ischemic brain damage and on blood-brain barrier permeability in the rat. QK administered by the intracerebroventricular, intravenous, or intranasal route caused a 40% decrease in ischemic brain damage induced by permanent occlusion of the middle cerebral artery relative to that in controls. No increase in the volume of the ischemic hemisphere compared to that of the contralateral nonischemic hemisphere was observed in rats treated with QK, suggesting that this peptide did not cause brain edema. The effect of QK on vessel permeability was evaluated by intravital pial microvessel videoimaging, a technique that allows the pial vessels to be visualized through a surgically prepared open cranial window. The results showed that QK did not cause any leakage of intravenously injected fluorescein-dextran conjugates after intracarotid administration or topical application to the brain cortex. Collectively, these data suggest that QK may exert neuroprotective activity in the context of stroke without promoting any increase in vascular permeability. Because VEGF's neuroprotective activity may be overshadowed by the appearance of brain edema and microbleeds, QK could represent a significant step forward in stroke treatment.
ACS Chem Neurosci 2015 Sep 16
PMID:Neuroprotective Effect of VEGF-Mimetic Peptide QK in Experimental Brain Ischemia Induced in Rat by Middle Cerebral Artery Occlusion. 2617 41

Traumatic brain injury (TBI) is a devastating actuality in clinics worldwide. It is estimated that approximately 10 million people among the world suffer from TBI each year, and a considerable number of patients will be temporarily or permanently disabled or even die due to this disease. Astrocytes play a very important role in the repair of brain tissue after TBI, including the formation of a neuroprotective barrier, inhibition of brain edema, and inhibition of normal nerve cell apoptosis. However, the detailed mechanism underlying this protective effect is still unclear. To investigate the regulatory factors of astrocytes to other neurons post-TBI, we established a TBI rat model and used the AAV to mediate the overexpression of GJA1-20k in astrocytes of rats. And functionally, the specific overexpression of GJA1-20k in astrocytes promoted the viability and recovery of neurons in TBI. Mechanistically, the astrocytes-specific upregulation of GJA1-20k protected the function of mitochondria in neurons of FPI rats, thus suppressing the apoptosis of the damaged neurons. We hereby reported that astrocytes-specific overexpression of GJA1-20k enhanced the viability and recovery of the neurons in TBI through regulating their mitochondrial function.
ACS Chem Neurosci 2020 06 03
PMID:Overexpression of Astrocytes-Specific GJA1-20k Enhances the Viability and Recovery of the Neurons in a Rat Model of Traumatic Brain Injury. 3240 78

The newly highlighted research into programmed cell death (PCD), autophagy dependent cell death and pyroptotic cell death, has shown that these processes are both strongly correlated with the pathological progression of traumatic brain injury (TBI). However, their cross-talk in TBI remains unclear. Here, a moderate TBI model was established to explore the relationship between autophagy and pyroptosis. Rapamycin was used to activate the process of autophagy, which was impaired in the moderate TBI model, and this treatment reversed the expression of pyroptosis associated proteins, interleukin-13 (IL-13) and the pJAK-1 pathway, which were upregulated significantly after TBI. The level of IL-13 was downregulated, and the JAK-1 pathway was blocked to reveal the molecular mechanisms by which autophagy inhibits pyroptosis; these two treatments reduced the expression levels of pyroptosis associated proteins. In addition, these three interventions reduced the formation of neuronal NLRP3, the extent of brain edema, and the degree of cortical neuron degeneration. Furthermore, the deficit in motor function post-TBI was also markedly alleviated. Collectively, our results demonstrated that autophagy activation exerts a neuroprotective effect by inhibiting pyroptotic cell death in the moderate TBI model, and the inhibitory effect was dependent on the downregulation of IL-13 and repression of the JAK-1-STAT-1 signaling pathway.
ACS Chem Neurosci 2020 Nov 10
PMID:Autophagy Activation Represses Pyroptosis through the IL-13 and JAK1/STAT1 Pathways in a Mouse Model of Moderate Traumatic Brain Injury. 3317 Jun 12