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.
Keywords: Cholesterol, neurodegeneration, neurodevelopment, Rho GTPase, statins.
Current Molecular Pharmacology
Title:Mevalonate Cascade and Neurodevelopmental and Neurodegenerative Diseases: Future Targets for Therapeutic Application
Volume: 10
Author(s): Xiaodan Jiao, Niloufar Ashtari, Maryam Rahimi-Balaei, Qi Min Chen, Ilnaz Badbezanchi, Shahla Shojaei, Adel Marzban, Nima Mirzaei, Seunghyuk Chung, Teng Guan, Jiasi Li, Jerry Vriend, Shahram Ejtemaei Mehr, Jiming Kong and Hassan Marzban*
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
Keywords: Cholesterol, neurodegeneration, neurodevelopment, Rho GTPase, statins.
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.
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Cite this article as:
Jiao Xiaodan, Ashtari Niloufar, Rahimi-Balaei Maryam, Chen Min Qi, Badbezanchi Ilnaz, Shojaei Shahla, Marzban Adel, Mirzaei Nima, Chung Seunghyuk, Guan Teng, Li Jiasi, Vriend Jerry, Mehr Ejtemaei Shahram, Kong Jiming and Marzban Hassan*, Mevalonate Cascade and Neurodevelopmental and Neurodegenerative Diseases: Future Targets for Therapeutic Application, Current Molecular Pharmacology 2017; 10 (2) . https://dx.doi.org/10.2174/1874467209666160112125446
DOI https://dx.doi.org/10.2174/1874467209666160112125446 |
Print ISSN 1874-4672 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-4702 |
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Common mechanisms underpinning neurodevelopmental disorders and psychiatric diseases
A growing number of large-scale epidemiologic studies has strongly suggested that common mechanisms may be shared by aberrant brain development and psychiatric disorders. There is now an appreciation of synergic roles of genetic variants and environmental stress which profoundly affect the genome integrity and reshape brain development. This can lead ...read more
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