title: Mevalonate Cascade and Neurodevelopmental and Neurodegenerative Diseases: Future Targets for Therapeutic Application.
abstract: The mevalonate cascade is a key metabolic pathway that regulates a variety of cellular functions and is thereby implicated in the pathophysiology of most brain diseases, including neurodevelopmental and neurodegenerative disorders. Emerging lines of evidence suggest that statins and Rho GTPase inhibitors are efficacious and have advantageous properties in treatment of different pathologic conditions that are relevant to the central nervous system. Beyond the original role of statins in lowering cholesterol synthesis, they have anti-inflammatory, antioxidant and modulatory effects on signaling pathways. Additionally, Rho GTPase inhibitors and statins share the mevalonate pathway as a common target of their therapeutic actions. In this review, we discuss potential mechanisms through which these drugs, via their role in the mevalonate pathway, exert their neuroprotective effects in neurodegenerative and neurodevelopmental disorders.
authors.affiliation: Department of Human Anatomy and Cell Science, Manitoba Institute of Child Health (MICH), Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Department of Human Anatomy and Cell Science, Manitoba Institute of Child Health (MICH), Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Niloufar
authors.initials: N
authors.lastname: Ashtari
authors.affiliation: Department of Human Anatomy and Cell Science, Manitoba Institute of Child Health (MICH), Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rahimi-Balaei
authors.affiliation: Department of Human Anatomy and Cell Science, Manitoba Institute of Child Health (MICH), Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Qi Min
authors.initials: QM
authors.lastname: Chen
authors.affiliation: Department of Human Anatomy and Cell Science, Manitoba Institute of Child Health (MICH), Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Ilnaz
authors.initials: I
authors.lastname: Badbezanchi
authors.affiliation: Department of Clinical Biochemistry, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Shahla
authors.initials: S
authors.lastname: Shojaei
authors.affiliation: Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Adel
authors.initials: A
authors.lastname: Marzban
authors.affiliation: Department of Human Anatomy and Cell Science, Manitoba Institute of Child Health (MICH), Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Nima
authors.initials: N
authors.lastname: Mirzaei
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Illinois at Chicago, Chicago, IL 60612, United States.
authors.forename: Seunghyuk
authors.initials: S
authors.lastname: Chung
authors.affiliation: Department of Human Anatomy and Cell Science, Manitoba Institute of Child Health (MICH), Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Teng
authors.initials: T
authors.lastname: Guan
authors.affiliation: Department of Human Anatomy and Cell Science, Manitoba Institute of Child Health (MICH), Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Jiasi
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Human Anatomy and Cell Science, Manitoba Institute of Child Health (MICH), Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Jerry
authors.initials: J
authors.lastname: Vriend
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shahram Ejtemaei
authors.initials: SE
authors.lastname: Mehr
authors.affiliation: Department of Human Anatomy and Cell Science, Manitoba Institute of Child Health (MICH), Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Jiming
authors.initials: J
authors.lastname: Kong
authors.affiliation: Department of Human Anatomy and Cell Science, Rm129, BMSB, 745 Bannatyne Avenue, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada.
authors.forename: Hassan
authors.initials: H
authors.lastname: Marzban
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008798:Mevalonic Acid / Q000378:metabolism* / Q000494:pharmacology; D054259:Neural Tube / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D020741:rho GTP-Binding Proteins; D008798:Mevalonic Acid
keywords: Cholesterol; Rho GTPase; neurodegeneration; neurodevelopment; statins