دورية أكاديمية
أعرض في EDS

GDNF-mediated rescue of the nigrostriatal system depends on the degree of degeneration.

التفاصيل البيبلوغرافية
العنوان: GDNF-mediated rescue of the nigrostriatal system depends on the degree of degeneration.
المؤلفون: Quintino L; CNS Gene Therapy, Department of Experimental Medical Science, Lund University, Lund, Sweden., Avallone M; CNS Gene Therapy, Department of Experimental Medical Science, Lund University, Lund, Sweden., Brännstrom E; CNS Gene Therapy, Department of Experimental Medical Science, Lund University, Lund, Sweden., Kavanagh P; CNS Gene Therapy, Department of Experimental Medical Science, Lund University, Lund, Sweden., Lockowandt M; CNS Gene Therapy, Department of Experimental Medical Science, Lund University, Lund, Sweden., Garcia Jareño P; CNS Gene Therapy, Department of Experimental Medical Science, Lund University, Lund, Sweden., Breger LS; CNS Gene Therapy, Department of Experimental Medical Science, Lund University, Lund, Sweden., Lundberg C; CNS Gene Therapy, Department of Experimental Medical Science, Lund University, Lund, Sweden. Cecilia.lundberg@med.lu.se.
المصدر: Gene therapy [Gene Ther] 2019 Feb; Vol. 26 (1-2), pp. 57-64. Date of Electronic Publication: 2018 Dec 07.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9421525 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5462 (Electronic) Linking ISSN: 09697128 NLM ISO Abbreviation: Gene Ther Subsets: MEDLINE
أسماء مطبوعة: Publication: London : Nature Publishing Group
Original Publication: Houndmills, Basingstoke, Hampshire, UK : Macmillan Press Ltd., c1994-
مواضيع طبية MeSH: Genetic Therapy/*methods , Glial Cell Line-Derived Neurotrophic Factor/*genetics , Parkinson Disease/*therapy , Striatonigral Degeneration/*therapy, Animals ; Female ; Glial Cell Line-Derived Neurotrophic Factor/metabolism ; Lentivirus/genetics ; Oxidopamine/toxicity ; Parkinson Disease/etiology ; Rats ; Rats, Sprague-Dawley ; Striatonigral Degeneration/etiology ; Substantia Nigra/metabolism ; Substantia Nigra/pathology
مستخلص: Glial cell-line derived neurotrophic factor (GDNF) is a promising therapeutic molecule to treat Parkinson's disease. Despite an excellent profile in experimental settings, clinical trials testing GDNF have failed. One of the theories to explain these negative outcomes is that the clinical trials were done in late-stage patients that have advanced nigrostriatal degeneration and may therefore not respond to a neurotrophic factor therapy. Based on this idea, we tested if the stage of nigrostriatal degeneration is important for GDNF-based therapies. Lentiviral vectors expressing regulated GDNF were delivered to the striatum of rats to allow GDNF expression to be turned on either while the nigrostriatal system was degenerating or after the nigrostriatal system had been fully lesioned by 6-OHDA. In the group of animals where GDNF expression was on during degeneration, neurons were rescued and there was a reversal of motor deficits. Turning GDNF expression on after the nigrostriatal system was lesioned did not rescue neurons or reverse motor deficits. In fact, these animals were indistinguishable from the control groups. Our results suggest that GDNF can reverse motor deficits and nigrostriatal pathology despite an ongoing nigrostriatal degeneration, if there is still a sufficient number of remaining neurons to respond to therapy.
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المشرفين على المادة: 0 (Glial Cell Line-Derived Neurotrophic Factor)
8HW4YBZ748 (Oxidopamine)
تواريخ الأحداث: Date Created: 20181212 Date Completed: 20190411 Latest Revision: 20200225
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6514883
DOI: 10.1038/s41434-018-0049-0
PMID: 30531868
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-5462
DOI:10.1038/s41434-018-0049-0