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      Isoprenoids and Protein Prenylation: Implications in the Pathogenesis and Therapeutic Intervention of Alzheimer’s Disease

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          Abstract

          The mevalonate-isoprenoid-cholesterol biosynthesis pathway plays a key role in human health and disease. The importance of this pathway is underscored by the discovery that two major isoprenoids, farnesyl and geranylgeranyl pyrophosphate, are required to modify an array of proteins through a process known as protein prenylation, catalyzed by prenyltransferases. The lipophilic prenyl group facilitates the anchoring of proteins in cell membranes, mediating protein-protein interactions and signal transduction. Numerous essential intracellular proteins undergo prenylation, including most members of the small GTPase superfamily as well as heterotrimeric G proteins and nuclear lamins, and are involved in regulating a plethora of cellular processes and functions. Dysregulation of isoprenoids and protein prenylation is implicated in various disorders, including cardiovascular and cerebrovascular diseases, cancers, bone diseases, infectious diseases, progeria, and neurodegenerative diseases including Alzheimer’s disease. Therefore, isoprenoids and/or prenyltransferases have emerged as attractive targets for developing therapeutic agents. Here, we provide a general overview of isoprenoid synthesis, the process of protein prenylation and the complexity of prenylated proteins, and pharmacological agents that regulate isoprenoids and protein prenylation. Recent findings that connect isoprenoids/protein prenylation with Alzheimer’s disease are summarized and potential applications of new prenylomic technologies for uncovering the role of prenylated proteins in the pathogenesis of Alzheimer’s disease are discussed.

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          Author and article information

          Journal
          8903774
          3208
          Crit Rev Biochem Mol Biol
          Crit. Rev. Biochem. Mol. Biol.
          Critical reviews in biochemistry and molecular biology
          1040-9238
          1549-7798
          1 August 2018
          June 2018
          01 June 2019
          : 53
          : 3
          : 279-310
          Affiliations
          [1 ]Departments of Experimental and Clinical Pharmacolog,University of Minnesota, Minneapolis, MN 55455
          [2 ]Departments of Chemistry,University of Minnesota, Minneapolis, MN 55455
          [3 ]Departments of Pharmacology, University of Minnesota, Minneapolis, MN 55455
          Author notes
          [* ]Corresponding Authors: Ling Li, lil@ 123456umn.edu ; Mark Distefano, diste001@ 123456umn.edu
          Article
          PMC6101676 PMC6101676 6101676 nihpa983435
          10.1080/10409238.2018.1458070
          6101676
          29718780
          Categories
          Article

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