title: siRNA as a tool to improve the treatment of brain diseases: Mechanism, targets and delivery.
abstract: As the population ages, brain pathologies such as neurodegenerative diseases and brain cancer increase their incidence, being the need to find successful treatments of upmost importance. Drug delivery to the central nervous system (CNS) is required in order to reach diseases causes and treat them. However, biological barriers, mainly blood-brain barrier (BBB), are the key obstacles that prevent the effectiveness of possible treatments due to their ability to strongly limit the perfusion of compounds into the brain. Over the past decades, new approaches towards overcoming BBB and its efflux transporters had been proposed. One of these approaches here reviewed is through small interfering RNA (siRNA), which is capable to specifically target one gene and silence it in a post-transcriptional way. There are different possible functional proteins at the BBB, as the ones responsible for transport or just for its tightness, which could be a siRNA target. As important as the effective silence is the way to delivery siRNA to its anatomical site of action. This is where nanotechnology-based systems may help, by protecting siRNA circulation and providing cell/tissue-targeting and intracellular siRNA delivery. After an initial overview on incidence of brain diseases and basic features of the CNS, BBB and its efflux pumps, this review focuses on recent strategies to reach brain based on siRNA, and how to specifically target these approaches in order to treat brain diseases.
authors: INEB - Instituto de Engenharia Biomédica, Biocarrier Group, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.
authors: Maria João
authors: MJ
authors: Gomes
authors: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense, Denmark.
authors: Susana
authors: S
authors: Martins
authors: INEB - Instituto de Engenharia Biomédica, Biocarrier Group, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal. Electronic address: bruno.sarmento@ineb.up.pt.
authors: Bruno
authors: B
authors: Sarmento
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001927:Brain Diseases / Q000188:drug therapy*; D016503:Drug Delivery Systems; D006801:Humans; D034741:RNA, Small Interfering
chemical_list: D034741:RNA, Small Interfering
keywords: Blood–brain barrier; Brain diseases; Efflux transporters; Nanoparticles; siRNA