Approches de<i>gene silencing</i>pour le traitement de la maladie de Huntington

Mérienne, Nicolas; Déglon, Nicole

doi:10.1051/medsci/20153102012

Cited by 3 publications

(1 citation statement)

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“…Lentiviral vectors can allow stable and long-term expression of transgenes in non-mitotic cells, which have been widely utilized in neurological diseases 29 . For example, SiRNA treatment for Parkinson's disease 30 , Huntington's disease 31 and Alzheimer's disease 32 are in the preclinical stage of research. Lentiviral vectors have already undergone relevant clinical trials in HIV, thalassemia, X-linked adrenoleukodystrophy (ALD), and early-onset metachromatic leukodystrophy (MLD), without serious adverse events 33 .…”

Section: Introductionmentioning

confidence: 99%

Reduction of depression-like behavior in rat model induced by ShRNA targeting norepinephrine transporter in locus coeruleus

Yin

Yuan

et al. 2020

Transl Psychiatry

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Depression may be associated with reduced monoamine neurotransmission, particularly serotonin and norepinephrine (NE). Reuptake of NE by the norepinephrine transporter (NET) is the primary mechanism by which many of the antidepressants are high-affinity substrates for NET. This study aimed to examine the effect of lentivirus-mediated shRNA targeting NET in locus coeruleus (LC) on depression-like behaviors of rats. We randomly assigned 60 male Wistar rats to 6 experimental groups: (1) Control group: without chronic unpredictable mild stress (CUMS) and without NET-shRNA treatment; (2) shRNA group: without CUMS + NET-shRNA; (3) CUMS group: 3-week CUMS without NET-shRNA; (4) CUMS + nonsense shRNA group; (5) CUMS + amygdala (Amy)-shRNA group; (6) CUMS+ locus coeruleus (LC)-shRNA group. First, recombinant lentiviral vector expressing shRNA (ShRNA-629, ShRNA-330, ShRNA-1222, ShRNA-1146 or ShRNA- negative control) against NET were produced, and their efficiency in knocking down of NET in PC12 cells were assessed by Q-PCR and western blot analysis. Second, shRNA was injected into the rat LC bilaterally to investigate whether it could prevent the depressive-like behavior induced by 3-week CUMS. Third, we tested the depressive-like behavior of the rats in the forced swimming test, the open field test, the sucrose preference test, as well as the body weight gain at the end of the seventh week. Finally, the protein expressions of NET was measured by western blot and the NE levels were measured by high performance liquid chromatography. Q-PCR and western blot showed that the ShRNA-1146 had the best interference efficiency targeting on NET in PC12 cells (p < 0.01). Compared to the depression model group, the immobility time in the forced swimming test was significantly reduced (p < 0.01), but the sucrose preference and the total scores in the open field test were significantly increased (all p < 0.01) in the group treated with shRNA in LC. Furthermore, compared with the depression model group, NET levels were significantly decreased (p < 0.01), but NE levels were significantly increased in the group treated with shRNA in LC (p < 0.05). Our findings suggest that Lentivirus-mediated shRNA targeting NET in LC downregulated NET both in vitro and in vivo, resulting in a significant decrease in depressive-like behavior of rats.

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Section: Introductionmentioning

confidence: 99%

Reduction of depression-like behavior in rat model induced by ShRNA targeting norepinephrine transporter in locus coeruleus

Yin

Yuan

et al. 2020

Transl Psychiatry

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Natural Products against Huntington's Disease (HD): Implications of Neurotoxic Animal Models and Transgenics in Preclinical Studies

Dey

2017

Neuroprotective Natural Products

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Clinical Gene Therapy for Neurodegenerative Diseases: Past, Present, and Future

2017

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Clinical gene therapy has made important advances over the last decade. Among neurological diseases, severe genetic neurodegenerative conditions have been the focus of initial clinical applications. Gene therapy has also addressed complex neurodegenerative diseases, particularly Parkinson's disease, with encouraging results in human patients, demonstrating that specific targeting of central nervous system (CNS) cells is a relevant strategy for severe pathologies and that efficient access to the CNS with viral vectors is an achievable goal. The purpose of this review is to summarize the gene therapy clinical applications that have been conducted for neurodegenerative diseases. Limitations and hurdles to obtain and demonstrate benefit in patients, and the new developments that should allow new clinical applications with high beneficial potential are discussed.

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Approches degene silencingpour le traitement de la maladie de Huntington

Cited by 3 publications

References 44 publications

Reduction of depression-like behavior in rat model induced by ShRNA targeting norepinephrine transporter in locus coeruleus

Reduction of depression-like behavior in rat model induced by ShRNA targeting norepinephrine transporter in locus coeruleus

Natural Products against Huntington's Disease (HD): Implications of Neurotoxic Animal Models and Transgenics in Preclinical Studies

Clinical Gene Therapy for Neurodegenerative Diseases: Past, Present, and Future

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