ABC transporters and cytochromes P450 in the human central nervous system: influence on brain pharmacokinetics and contribution to neurodegenerative disorders.
BACKGROUND
The identification of xenobiotic metabolizing enzymes (i.e., CYP) and transporters (i.e., ABC transporters) (XMET) in the human brain, including the BBB, raises the question whether these transporters and enzymes have specific functions in brain physiology, neuropharmacology and toxicology.


METHODS
Relevant literature was identified using PubMed search articles published up to March 2010. Search terms included 'ABC transporters and P450 or CYP', 'drug metabolism, effect and toxicity' and 'neurodegenerative disease (Alzheimer and Parkinson diseases)' restricted to the field of 'brain or human brain'.


RESULTS
This review aims to provide a better understanding of XMET functions in the human brain and show their pharmacological importance for improving drug delivery and efficacy and also for managing their side effects. Finally, the impact of brain XMET activity during neurodegenerative processes is discussed, giving an opportunity to identify new markers of human brain diseases.


CONCLUSIONS
During the last 2 decades, much evidence concerning the specific distribution patterns of XMET, their induction by xenobiotics and endobiotics and their genetic variations have made cerebral ABC transporters and CYP enzymes key elements in the way individual patients respond to centrally acting drugs.
Dutheil
Fabien
F
Université Paris Descartes, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France.
Jacob
Aude
A
Dauchy
Sandrine
S
Beaune
Philippe
P
Scherrmann
Jean-Michel
JM
Declèves
Xavier
X
Loriot
Marie-Anne
MA
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000503:physiopathology; D015262:Xenobiotics / Q000009:adverse effects / Q000493:pharmacokinetics*
D018528:ATP-Binding Cassette Transporters; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System