Cytochrome P450 in Neurological Disease

M.      Liu; P.   D.   Hurn; N.   J.   Alkayed

doi:10.2174/1389200043335540

Abstract

Advances in a multitude of disciplines support an emerging role for cytochrome P450 enzymes and their metabolic substrates and end-products in the pathogenesis and treatment of central nervous system disorders, including acute cerebrovascular injury, such as stroke, chronic neurodegenerative disease, such as Alzheimers and Parkinsons disease, as well as epilepsy, multiple sclerosis and psychiatric disorders, including anxiety and depression. The neural tissue contains its own unique set of P450 genes that are regulated in a manner that is distinct from their molecular regulation in peripheral tissue. Furthermore, brain P450s catalyze the formation of important brain signaling molecules, such as neurosteroids and eicosanoids, and metabolize substrates as diverse as vitamins A and D, cholesterol, bile acids, as well as centrally acting drugs, anesthetics and environmental neurotoxins. These unique characteristics allow this family of proteins and their metabolites to perform such vital functions in brain as neurotrophic support, neuroprotection, control of cerebral blood flow, temperature control, neuropeptide release, maintenance of brain cholesterol homoeostasis, elimination of retinoids from CNS, regulation of neurotransmitter levels and other functions important in brain physiology, development and disease.

Keywords: cytochrome p450, eicosanoids, eets, neurosteroids, estrogen, cerebral ischemia, preconditioning, neuroprotection