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.
