ABSTRACT
The treatment of brain tumors and neurodegenerative diseases, represents an ongoing challenge. In Central Nervous System (CNS) the achievement of therapeutic concentration of chemical agents is complicated by the presence of distinct set of efflux proteins, such as ATP-Binding Cassette (ABC) transporters localized on the Blood-Brain Barrier (BBB). The activity of ABC transporters seems to be a common mechanism that underlies the poor response of CNS diseases to therapies. The molecular characterization of Breast Cancer Resistance Protein (BCRP/ABCG2), as an ABC transporter conferring multidrug resistance (MDR), has stimulated many studies to investigate its activity on the BBB, its involvement in physiology and CNS diseases and its role in limiting the delivery of drugs in CNS. In this review, we highlight the activity and localization of BCRP on the BBB and the action that this efflux pump has on many conventional drugs or latest generation molecules used for the treatment of CNS tumors and other neurodegenerative diseases.
Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism , Blood-Brain Barrier , Central Nervous System Neoplasms/therapy , Neoplasm Proteins/metabolism , Neurodegenerative Diseases/therapy , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/therapeutic use , Central Nervous System Neoplasms/metabolism , Humans , Neurodegenerative Diseases/metabolism , Nootropic Agents/pharmacokinetics , Nootropic Agents/therapeutic use , Tissue DistributionABSTRACT
ß-adrenergic receptors (ß-ARs) are G protein-coupled receptors that activate signal transduction pathways involved in angiogenesis, resulting in enhanced tumor vascularization and more aggressive growth. In this study, we evaluated the expression of ß-ARs in a population of 12 children affected by malignant primary brain tumors. We found a significant expression of ß1- and ß2-ARs in all 12 samples as well as the 3 cell lines tested (U87MG, T98G and DAOY). The mean absolute ß1-AR mRNA level standardized to GAPDH was 5.81 (range, -7.91 to 11.29) for brain tumors and 8.59 (range, 6.046 to 12.59) for cell lines (U87MG, DAOY and T98G), respectively. The mean absolute ß2-AR mRNA level was 4.74 (range, -9.30 to 8.45) for tumor specimens and 7.64 (range, 5.85 to 8.88) for cell lines. These real-time quantitative (qRT)-PCR expression data were confirmed by immunohistochemical analysis. Our study evaluated the presence of ß1- and ß2-ARs in malignant pediatric brain tumors and brain tumor cell lines.
