LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 3 of total 3

Search options

  1. Article ; Online: TRPM7 in cerebral ischemia and potential target for drug development in stroke.

    Bae, Christine You-jin / Sun, Hong-shuo

    Acta pharmacologica Sinica

    2011  Volume 32, Issue 6, Page(s) 725–733

    Abstract: ... which may also cause ionic imbalance and cell death in cerebral ischemia. Transient receptor potential melastatin ... in physiology and pathophysiology as well as its therapeutic potential in stroke. ... cerebral ischemia. In this review, we will discuss the current understanding of the role of TRPM7 channels ...

    Abstract Searching for effective pharmacological agents for stroke treatment has largely been unsuccessful. Despite initial excitement, antagonists for glutamate receptors, the most studied receptor channels in ischemic stroke, have shown insufficient neuroprotective effects in clinical trials. Outside the traditional glutamate-mediated excitotoxicity, recent evidence suggests few non-glutamate mechanisms, which may also cause ionic imbalance and cell death in cerebral ischemia. Transient receptor potential melastatin 7 (TRPM7) is a Ca(2+) permeable, non-selective cation channel that has recently gained attention as a potential cation influx pathway involved in ischemic events. Compelling new evidence from an in vivo study demonstrated that suppression of TRPM7 channels in adult rat brain in vivo using virally mediated gene silencing approach reduced delayed neuronal cell death and preserved neuronal functions in global cerebral ischemia. In this review, we will discuss the current understanding of the role of TRPM7 channels in physiology and pathophysiology as well as its therapeutic potential in stroke.
    MeSH term(s) Animals ; Brain Ischemia/drug therapy ; Brain Ischemia/etiology ; Brain Ischemia/metabolism ; Drug Discovery ; Gene Silencing ; Humans ; Protein-Serine-Threonine Kinases ; RNA, Small Interfering/therapeutic use ; Stroke/drug therapy ; Stroke/etiology ; Stroke/metabolism ; TRPM Cation Channels/antagonists & inhibitors ; TRPM Cation Channels/genetics ; TRPM Cation Channels/physiology
    Chemical Substances RNA, Small Interfering ; TRPM Cation Channels ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; TRPM7 protein, human (EC 2.7.11.1)
    Language English
    Publishing date 2011-05-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1360774-1
    ISSN 1745-7254 ; 0253-9756 ; 1671-4083
    ISSN (online) 1745-7254
    ISSN 0253-9756 ; 1671-4083
    DOI 10.1038/aps.2011.60
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1904: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Waixenicin A, a marine-derived TRPM7 inhibitor: a promising CNS drug lead.

    Sun, Hong-Shuo / Horgen, F David / Romo, Daniel / Hull, Kenneth G / Kiledal, Sigrid A / Fleig, Andrea / Feng, Zhong-Ping

    Acta pharmacologica Sinica

    2020  Volume 41, Issue 12, Page(s) 1519–1524

    Abstract: ... We here suggest that TRPM7 is an emerging drug target for CNS diseases and disorders, and waixenicin A is ... potential (TRP) family, namely the melastatin subfamily member 7 (TRPM7), as an emerging drug target. TRPM7 ... brain injury, and is one of the key nonglutamate mechanisms in cerebral ischemia and stroke. Currently ...

    Abstract Ion channels are the third largest class of targets for therapeutic drugs. The pharmacology of ion channels is an important research area for identifying new treatment options for human diseases. The past decade or so has seen increasing interest in an ion channel protein belonging to the transient receptor potential (TRP) family, namely the melastatin subfamily member 7 (TRPM7), as an emerging drug target. TRPM7 is a bifunctional protein with a magnesium and calcium-conducting divalent ion channel fused with an active kinase domain. TRPM7 is ubiquitously expressed in human tissues, including the brain, and regulates various cell biology processes such as magnesium and calcium homeostasis, cell growth and proliferation, and embryonic development. TRPM7 provides a link between cellular metabolic status and intracellular calcium homeostasis in neurons due to TRPM7's unique sensitivity to fluctuating intracellular Mg·ATP levels. Thus, the protein plays a key role in ischemic and hypoxic neuronal cell death and brain injury, and is one of the key nonglutamate mechanisms in cerebral ischemia and stroke. Currently, the most potent and specific TRPM7 inhibitor is waixenicin A, a xenicane diterpenoid from the Hawaiian soft coral Sarcothelia edmondsoni. Using waixenicin A as a pharmacological tool, we demonstrated that TRPM7 is involved in promoting neurite outgrowth in vitro. Most recently, we found that waixenicin A reduced hypoxic-ischemic brain injury and preserved long-term behavioral outcomes in mouse neonates. We here suggest that TRPM7 is an emerging drug target for CNS diseases and disorders, and waixenicin A is a viable drug lead for these disorders.
    MeSH term(s) Acetates/pharmacology ; Acetates/therapeutic use ; Animals ; Cell Line ; Central Nervous System Agents/pharmacology ; Central Nervous System Agents/therapeutic use ; Diterpenes/pharmacology ; Diterpenes/therapeutic use ; Humans ; Hypoxia-Ischemia, Brain/drug therapy ; TRPM Cation Channels/antagonists & inhibitors
    Chemical Substances Acetates ; Central Nervous System Agents ; Diterpenes ; TRPM Cation Channels ; waixenicin A
    Language English
    Publishing date 2020-09-29
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1360774-1
    ISSN 1745-7254 ; 0253-9756 ; 1671-4083
    ISSN (online) 1745-7254
    ISSN 0253-9756 ; 1671-4083
    DOI 10.1038/s41401-020-00512-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1904: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: TRPM7 Mediates Neuronal Cell Death Upstream of Calcium/Calmodulin-Dependent Protein Kinase II and Calcineurin Mechanism in Neonatal Hypoxic-Ischemic Brain Injury.

    Turlova, Ekaterina / Wong, Raymond / Xu, Baofeng / Li, Feiya / Du, Lida / Habbous, Steven / Horgen, F David / Fleig, Andrea / Feng, Zhong-Ping / Sun, Hong-Shuo

    Translational stroke research

    2020  Volume 12, Issue 1, Page(s) 164–184

    Abstract: ... therapeutic and drug development target for HIE. ... CaMKII) and phosphatase calcineurin as potential mediators of cell death downstream from TRPM7 activation ... ion channel, is critical for axonal development, and mediates hypoxic and ischemic neuronal cell death ...

    Abstract Transient receptor potential melastatin 7 (TRPM7), a calcium-permeable, ubiquitously expressed ion channel, is critical for axonal development, and mediates hypoxic and ischemic neuronal cell death in vitro and in vivo. However, the downstream mechanisms underlying the TRPM7-mediated processes in physiology and pathophysiology remain unclear. In this study, we employed a mouse model of hypoxic-ischemic brain cell death which mimics the pathophysiology of hypoxic-ischemic encephalopathy (HIE). HIE is a major public health issue and an important cause of neonatal deaths worldwide; however, the available treatments for HIE remain limited. Its survivors face life-long neurological challenges including mental retardation, cerebral palsy, epilepsy and seizure disorders, motor impairments, and visual and auditory impairments. Through a proteomic analysis, we identified calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphatase calcineurin as potential mediators of cell death downstream from TRPM7 activation. Further analysis revealed that TRPM7 mediates cell death through CaMKII, calmodulin, calcineurin, p38, and cofilin cascade. In vivo, we found a significant reduction of brain injury and improvement of short- and long-term functional outcomes after HI after administration of specific TRPM7 blocker waixenicin A. Our data demonstrate a molecular mechanism of TRPM7-mediated cell death and identifies TRPM7 as a promising therapeutic and drug development target for HIE.
    MeSH term(s) Acetates/pharmacology ; Animals ; Animals, Newborn ; Avoidance Learning/physiology ; Calcineurin/metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism ; Cell Death/drug effects ; Cell Death/physiology ; Cells, Cultured ; Diterpenes/pharmacology ; Female ; HEK293 Cells ; Humans ; Hypoxia-Ischemia, Brain/metabolism ; Hypoxia-Ischemia, Brain/pathology ; Male ; Mice ; Neurons/drug effects ; Neurons/metabolism ; Neurons/pathology ; TRPM Cation Channels/metabolism
    Chemical Substances Acetates ; Diterpenes ; TRPM Cation Channels ; waixenicin A ; Trpm7 protein, mouse (EC 2.7.1.-) ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 (EC 2.7.11.17) ; Calcineurin (EC 3.1.3.16)
    Language English
    Publishing date 2020-05-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2541897-X
    ISSN 1868-601X ; 1868-4483
    ISSN (online) 1868-601X
    ISSN 1868-4483
    DOI 10.1007/s12975-020-00810-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top