title: Development of Nonviral Vectors Targeting the Brain as a Therapeutic Approach For Parkinson's Disease and Other Brain Disorders.
abstract: Parkinson's disease (PD) is a debilitating neurodegenerative disease characterized by tremor, rigidity, bradykinesia, and postural instability, for which there is no effective treatment available till date. Here, we report the development of nonviral vectors specific for neuronal cells that can deliver short interfering RNA (siRNA) against the α-synuclein gene (SNCA), and prevent PD-like symptoms both in vitro and in vivo. These vectors not only help siRNA duplexes cross the blood-brain barrier in mice, but also stabilize these siRNAs leading to a sustainable 60-90% knockdown of α-synuclein protein. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine rapidly develop PD-like symptoms which were significantly alleviated when SNCA was knocked down using our vectors. Together, our data not only confirm the central role of α-synuclein in the onset of PD, but also provide a proof of principle that these nonviral vectors can be used as novel tools to design effective strategies to combat central nervous system diseases.
authors.affiliation: Department of Biochemistry, College of Medicine and Health Science, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Hayate
authors.initials: H
authors.lastname: Javed
authors.affiliation: Department of Biochemistry, College of Medicine and Health Science, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Sindhu A
authors.initials: SA
authors.lastname: Menon
authors.affiliation: Department of Biochemistry, College of Medicine and Health Science, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Karima M
authors.initials: KM
authors.lastname: Al-Mansoori
authors.affiliation: Department of Biochemistry, College of Medicine and Health Science, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Abdelmojib
authors.initials: A
authors.lastname: Al-Wandi
authors.affiliation: Department of Biochemistry, College of Medicine and Health Science, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Nour K
authors.initials: NK
authors.lastname: Majbour
authors.affiliation: Department of Biochemistry, College of Medicine and Health Science, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Mustafa T
authors.initials: MT
authors.lastname: Ardah
authors.affiliation: Department of Biochemistry, College of Medicine and Health Science, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Shiji
authors.initials: S
authors.lastname: Varghese
authors.affiliation: Department of Biochemistry, College of Medicine and Health Science, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Nishant N
authors.initials: NN
authors.lastname: Vaikath
authors.affiliation: Department of Biochemistry, College of Medicine and Health Science, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: M Emdadul
authors.initials: ME
authors.lastname: Haque
authors.affiliation: Department of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.
authors.forename: Mimoun
authors.initials: M
authors.lastname: Azzouz
authors.affiliation: Neurological Disorders Center, Qatar Biomedical Research Institute, and College of Science and Engineering, Hamad Bin Khalifa University (HBKU), Education City, Qatar Foundation, P.O. Box 5825 Doha, Qatar. Electronic address: oelagnaf@qf.org.qa.
authors.forename: Omar Ma
authors.initials: OM
authors.lastname: El-Agnaf
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002460:Cell Line; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D051379:Mice; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics / Q000628:therapy*; D019151:Peptide Library; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D051844:alpha-Synuclein / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D019151:Peptide Library; D034741:RNA, Small Interfering; C497605:Snca protein, mouse; D051844:alpha-Synuclein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine