• Libraries
    • Log in to:
    View Item 
    •   MSpace Home
    • University of Manitoba Researchers
    • University of Manitoba Scholarship
    • View Item
    •   MSpace Home
    • University of Manitoba Researchers
    • University of Manitoba Scholarship
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Targeting the Mevalonate Cascade as a New Therapeutic Approach in Heart Disease, Cancer and Pulmonary Disease

    Thumbnail
    View/Open
    Ghavami-Zeki-Phar Ther-2014.pdf (834.8Kb)
    Date
    2014-02-26
    Author
    Yeganeh, Behzad
    Wiechec, Emmilia
    Ande, Sudharsana
    Sharma, Pawan
    Moghadam, Adel Rezaei
    Post, Martin
    Freed, Darren H.
    Hashemi, Mohammad
    Shojaei, Shahla
    Zeki, Amir A.
    Ghavami, Saeid
    Metadata
    Show full item record
    Abstract
    The cholesterol biosynthesis pathway, also known as the mevalonate (MVA) pathway, is an essential cellular pathway that is involved in diverse cell functions. The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) is the rate-limiting step in cholesterol biosynthesis and catalyzes the conversion of HMG-CoA to MVA. Given its role in cholesterol and isoprenoid biosynthesis, the regulation of HMGCR has been intensely investigated. Because all cells require a steady supply of MVA, both the sterol (i.e. cholesterol) and non-sterol (i.e. isoprenoid) products of MVA metabolism exert coordinated feedback regulation on HMGCR through different mechanisms. The proper functioning of HMGCR as the proximal enzyme in the MVA pathway is essential under both normal physiologic conditions and in many diseases given its role in cell cycle pathways and cell proliferation, cholesterol biosynthesis and metabolism, cell cytoskeletal dynamics and stability, cell membrance structure and fluidity, mitochondrial function, proliferation, and cell fate. The blockbuster statin drugs ('statins') directly bind to and inhibit HMGCR, and their use for the past thirty years has revolutionized the treatment of hypercholesterolemia and cardiovascular diseases, in particular coronary heart disease. Initially thought to exert their effects through cholesterol reduction, recent evidence indicates that statins also have pleiotropic immunomodulatory properties independent of cholesterol lowering. In this review we will focus on the therapeutic applications and mechanisms involved in the MVA cascade including Rho GTPase and Rho kinase (ROCK) signaling, statin inhibition of HMGCR, geranylgeranyltransferase (GGTase) inhibition, and farnesyltransferase (FTase) inhibition in cardiovascular disease, pulmonary diseases (e.g. asthma and chronic obstructive pulmonary disease (COPD), and cancer).
    URI
    http://hdl.handle.net/1993/23336
    DOI
    10.1016/j.pharmthera.2014.02.007
    Collections
    • Rady Faculty of Health Sciences Scholarly Works [1296]
    • University of Manitoba Scholarship [1952]

    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    Theme by 
    Atmire NV
     

     

    Browse

    All of MSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    Login

    Statistics

    View Usage Statistics

    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    Theme by 
    Atmire NV