Cytochrome P450 in the central nervous system as a therapeutic target in neurodegenerative diseases

Abstract

Cytochromes P450 (CYPs) constitute a family of enzymes that can be found in the endoplasmic reticulum (ER), mitochondria or the cell surface of the cells. CYPs are characterized by carrying out the oxidation of organic compounds and they are mainly recognized as mediators of the biotransformation of xenobiotics to polar hydrophilic metabolites that can be eliminated from the organism. However, these enzymes play a key role in many other physiological processes, being involved in diverse indispensable metabolic pathways since they metabolize many endogenous substrates. Various CYP isoforms are expressed in the brain, and it is believed that this could be in part due to the particular function of brain CYPs. In the brain, CYPs are involved in the cholesterol turnover, the biosynthesis of dopamine, serotonin, morphine, hormones, and protective lipid mediators (epoxyeicosatrienoic acids), in addition to their already recognized role in xenobiotics detoxification and psychotropic drug metabolism. Increasing evidence suggests that this group of enzymes is fundamental for the normal functioning and maintenance of brain homeostasis. This review is focused on highlighting the importance of CYP-mediated endogenous metabolism in the central nervous system (CNS) and its relationship with recent findings regarding CYP involvement in neurodegenerative diseases. Some therapeutic approaches focused on CYP regulation are also discussed.

Keywords:

• Cytochrome P450
• arachidonic acid
• cholesterol
• 24-hydroxycholesterol
• Alzheimer’s disease
• Parkinson’s disease

Disclosure statement

The authors declare that there are no conflicts of interest.

Additional information

Funding

Cynthia Navarro-Mabarak was supported by a CONACYT PhD fellowship No. [356644] to study in the program: Doctorado en Ciencias Biomédicas, Instituto de Investigaciones Biomédicas, UNAM.