AAV Vector-Mediated Gene Delivery to Substantia Nigra Dopamine Neurons : Implications for Gene Therapy and Disease Models

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dc.contributor.author Albert, Katrina
dc.contributor.author Voutilainen, Merja H.
dc.contributor.author Domanskyi, Andrii
dc.contributor.author Airavaara, Mikko
dc.date.accessioned 2017-05-10T13:34:01Z
dc.date.available 2017-05-10T13:34:01Z
dc.date.issued 2017-02
dc.identifier.citation Albert , K , Voutilainen , M H , Domanskyi , A & Airavaara , M 2017 , ' AAV Vector-Mediated Gene Delivery to Substantia Nigra Dopamine Neurons : Implications for Gene Therapy and Disease Models ' , Genes , vol. 8 , no. 2 , 63 . https://doi.org/10.3390/genes8020063
dc.identifier.other PURE: 84024171
dc.identifier.other PURE UUID: bab20eb2-7075-40c6-aa69-ccfd70a40ada
dc.identifier.other WOS: 000399058000018
dc.identifier.other Scopus: 85012247227
dc.identifier.other ORCID: /0000-0002-2026-1609/work/32700726
dc.identifier.uri http://hdl.handle.net/10138/183659
dc.description.abstract Gene delivery using adeno-associated virus (AAV) vectors is a widely used method to transduce neurons in the brain, especially due to its safety, efficacy, and long-lasting expression. In addition, by varying AAV serotype, promotor, and titer, it is possible to affect the cell specificity of expression or the expression levels of the protein of interest. Dopamine neurons in the substantia nigra projecting to the striatum, comprising the nigrostriatal pathway, are involved in movement control and degenerate in Parkinson's disease. AAV-based gene targeting to the projection area of these neurons in the striatum has been studied extensively to induce the production of neurotrophic factors for disease-modifying therapies for Parkinson's disease. Much less emphasis has been put on AAV-based gene therapy targeting dopamine neurons in substantia nigra. We will review the literature related to targeting striatum and/or substantia nigra dopamine neurons using AAVs in order to express neuroprotective and neurorestorative molecules, as well as produce animal disease models of Parkinson's disease. We discuss difficulties in targeting substantia nigra dopamine neurons and their vulnerability to stress in general. Therefore, choosing a proper control for experimental work is not trivial. Since the axons along the nigrostriatal tract are the first to degenerate in Parkinson's disease, the location to deliver the therapy must be carefully considered. We also review studies using AAV--synuclein (-syn) to target substantia nigra dopamine neurons to produce an -syn overexpression disease model in rats. Though these studies are able to produce mild dopamine system degeneration in the striatum and substantia nigra and some behavioural effects, there are studies pointing to the toxicity of AAV-carrying green fluorescent protein (GFP), which is often used as a control. Therefore, we discuss the potential difficulties in overexpressing proteins in general in the substantia nigra. en
dc.format.extent 15
dc.language.iso eng
dc.relation.ispartof Genes
dc.rights unspecified
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject adeno-associated virus
dc.subject alpha-synuclein
dc.subject Parkinson's disease
dc.subject substantia nigra
dc.subject dopamine
dc.subject neurotrophic factors
dc.subject GDNF
dc.subject striatum
dc.subject gene therapy
dc.subject GFP
dc.subject RAT MODEL
dc.subject VIRAL VECTORS
dc.subject 1184 Genetics, developmental biology, physiology
dc.title AAV Vector-Mediated Gene Delivery to Substantia Nigra Dopamine Neurons : Implications for Gene Therapy and Disease Models en
dc.type Review Article
dc.contributor.organization Institute of Biotechnology
dc.contributor.organization Regenerative Neuroscience
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.3390/genes8020063
dc.relation.issn 2073-4425
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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