Cristina Manuela Dragoi
Carol Davila University of Medicine and Pharmacy, Romania
Title: Blowing resistance to pharmacotherapy by modulating the permeability of the blood-brain barrier – patho-physiological perspectives
Biography
Biography: Cristina Manuela Dragoi
Abstract
The efficiency of the central nervous system disorders pharmacotherapy is a major challenge, mainly due to the impossibility of many drugs to cross the blood-brain barrier (BBB) and reach sufficiently high concentrations in certain target areas in the brain. The BBB possesses an outstanding ability to protect the brain against xenobiotics and potentially poisonous metabolites. Owing to this, ATP binding cassette (ABC) export proteins have gained tremendous interest in research. Of these efflux transporters of the blood-brain barrier, the most studied in terms of the mechanisms of action and regulatory effects, is the P-glycoprotein (Pgp, ABCB1), which modulates the transport of a large number of therapeutic substances and is predominantly expressed in the cerebral capillary endothelium. The action on the cerebral tissue and the beneficial effects of drugs or xenobiotics are dependent on their ability to cross the blood-brain barrier. ABC transporters represent an integral part of the human transportome and are of particular interest at the BBB as they significantly contribute to brain homeostasis. In addition, they appear to be involved in many CNS diseases. Therefore studying their mechanisms of action as well as their signaling cascades and responses to internal and external stimuli will help us understand the pathogenesis of these diseases. Signaling cascades underlying the expression and function of these proteins will be discussed as well as their role in diseases such as Alzheimer’s disease, epilepsy, amyotrophic lateral sclerosis and brain tumors.