siRNA as a tool to improve the treatment of brain diseases: Mechanism, targets and delivery

Ageing Research Reviews
Maria João GomesBruno Sarmento

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 i...Continue Reading

References

Jun 6, 2000·Advanced Drug Delivery Reviews·P B Watkins
Nov 22, 2000·The Journal of Cell Biology·A ZahraouiT Galli
Feb 28, 2002·Current Medicinal Chemistry·Carmen Avendaño, J Carlos Menéndez
Aug 17, 2002·Science·Greg Miller
Sep 18, 2002·The Journal of Pharmacology and Experimental Therapeutics·Georgy HartmannMicheline Piquette-Miller
Mar 15, 2003·Drug Metabolism Reviews·Mary Peace McRaeAngela D M Kashuba
May 14, 2003·The Journal of Cell Biology·Karl Matter, Maria S Balda
May 14, 2003·The Journal of Cell Biology·Takehiro NittaShoichiro Tsukita
Feb 5, 2004·FEBS Letters·Aleksandra Muratovska, Michael R Eccles
Mar 3, 2004·Molecular Interventions·William M Pardridge
Apr 3, 2004·Nature Reviews. Drug Discovery·Yair Dorsett, Thomas Tuschl
Apr 24, 2004·Genes & Development·Javier Martinez, Thomas Tuschl
Apr 28, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E M KemperO van Tellingen
Apr 28, 2004·Neurology·Felix SchlachetzkiWilliam M Pardridge
Jul 28, 2004·Trends in Pharmacological Sciences·Martin F Fromm
Sep 3, 2004·Bioorganic & Medicinal Chemistry Letters·Christina LorenzCarlo Unverzagt
Feb 18, 2005·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·William M Pardridge
Feb 22, 2005·Mini Reviews in Medicinal Chemistry·Karin Pleban, Gerhard F Ecker
May 26, 2005·Pharmacological Reviews·Brian T Hawkins, Thomas P Davis
Jun 1, 2005·Nature Genetics·Maria A ChristophorouGerard I Evan
Jul 14, 2005·Progress in Neurobiology·Wolfgang Löscher, Heidrun Potschka
Aug 17, 2005·Current Gene Therapy·Timothy M FountaineRichard Wade-Martins
Nov 22, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·E KleemannT Kissel
Dec 2, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·Grace H HuynhFrancis C Szoka
Dec 21, 2005·Biochemical and Biophysical Research Communications·Taro HinoHidehiro Mizusawa
May 6, 2006·Neuron·Chang-Hyuk KwonLuis F Parada
Nov 23, 2006·Blood Cells, Molecules & Diseases·John J TurnerMichael J Gait
Jan 16, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rong-Qin HuangChen Jiang
Jan 24, 2007·Journal of Controlled Release : Official Journal of the Controlled Release Society·Vijay A Sethuraman, You Han Bae
Feb 1, 2007·Nucleic Acids Research·Michael FisherPiet Herdewijn
Apr 24, 2007·Advanced Drug Delivery Reviews·Lars Aagaard, John J Rossi
Jun 5, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Isa E L M KuppensJan H M Schellens
Jun 8, 2007·Pharmaceutical Research·William M Pardridge
Jan 23, 2008·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Jamie L GilmoreAlexander V Kabanov
Apr 29, 2008·Journal of Neuroscience Research·Sujatha M GopalakrishnanUsha Warrior
May 30, 2008·The Journal of Gene Medicine·Matthew CampbellPeter Humphries
May 31, 2008·BMB Reports·Yoon Kyung Choi, Kyu-Won Kim
Dec 9, 2008·Biochimica Et Biophysica Acta·Nicolas WeissPierre-Olivier Couraud
Dec 10, 2008·Stroke; a Journal of Cerebral Circulation·Mark Fisher
Jul 28, 2009·Journal of Thrombosis and Haemostasis : JTH·N Mackman
Aug 15, 2009·Neuroscience Letters·Christina FuestHeidrun Potschka

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Citations

Mar 15, 2016·Acta Pharmacologica Sinica·Yuan-Yuan LiuHai-Rong Xiong
Oct 25, 2016·Materials Science & Engineering. C, Materials for Biological Applications·Danyang Wang, Lin-Ping Wu
Apr 16, 2016·Experimental Neurology·Ye Zhou, Lucia Notterpek
May 23, 2016·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Maria João GomesBruno Sarmento
Jul 28, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Carla L EspositoVittorio de Franciscis
Sep 7, 2016·Tissue Engineering. Part B, Reviews·Grace WaldenAram Saeed
Feb 2, 2017·Drug Development and Industrial Pharmacy·Oscar Escalona-RayoDavid Quintanar-Guerrero
Oct 19, 2019·Tissue Engineering and Regenerative Medicine·Sung Eun KimKyeongsoon Park
Apr 12, 2017·Topics in Current Chemistry·Yifei Lu, Chen Jiang
Sep 21, 2018·Experimental and Therapeutic Medicine·Wanliang Dong, Yuankun Zhang
Jan 4, 2020·Pharmaceutical Research·Christelle ZandanelChristine Vauthier
Sep 22, 2020·Current Opinion in Chemical Engineering·Alexander G SoretsEthan S Lippmann
Apr 2, 2021·Frontiers in Molecular Neuroscience·Kaushik BanerjeeMaria G Castro

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