Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenovirus is an efficient vector for neuronal gene therapy due to its ability to infect post-mitotic cells, its high efficacy of cell transduction and its low pathogenicity. Recombinant adenoviruses encoding for therapeutical agents can be delivered in vivo after direct intracerebral injection into specific brain areas. They can be transported in a retrograde manner from the injection site to the projection cell bodies offering promising applications for the specific targeting of selected neuronal populations not easily accessible by direct injection, such as the motor neurons in the spinal cord. Adenoviral vectors are also efficient tools for the ex vivo gene therapy, that is, the genetical modification of cells prior to their transplantation into the nervous system. Recently, the efficacy of the adenovirus as a gene vector system has been demonstrated in several models of neurodegenerative diseases including Parkinson's disease (PD) and motor neuron diseases. In rat models of PD, adenoviruses encoding for either tyrosine hydroxylase, superoxide dismutase or glial-derived neurotrophic factor improved the survival and the functional efficacy of dopaminergic cells. Similarly, the intramuscular injection of an adenovirus encoding for neurotrophin-3 had substantial therapeutic effects in a mutant mouse model of motor neuron degenerative disease. However, although adenoviruses are highly attractive for neuronal gene transfer, they can trigger a strong inflammatory reaction leading in particular to the destruction of infected cells. The recent development of new generations of adenoviral vectors could shed light on the nature of the immune reaction caused by adenoviral vectors in the brain. The use of these new vectors, combined with that of neurospecific and regulatable promoters, should improve adenovirus gene transfer into the central nervous system.
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PMID:Adenovirus in the brain: recent advances of gene therapy for neurodegenerative diseases. 965 83

The neurotrophin, brain derived neurotrophic factor (BDNF), exerts multiple effects on the development and maintenance of the nervous system, including regulating synaptic plasticity and promoting neuron survival. Here we report the selective failure of BDNF-dependent survival in cultured hippocampal neurons from the trisomy 16 (Ts16) mouse, an animal model of Down syndrome. This failure is accompanied by overexpression of a truncated, kinase-deficient isoform (T1) of the BDNF receptor tyrosine receptor kinase B (trkB). Adenovirus-mediated introduction of exogenous full-length trkB into Ts16 neurons fully restored BDNF-dependent survival, whereas exogenous truncated trkB expression in normal, euploid neurons reproduced the Ts16 BDNF signaling failure. Thus, the failure of Ts16 neurons to respond to BDNF is caused by dysregulation of trkB isoform expression. Such a neurotrophin signaling defect could contribute to developmental and degenerative disorders of the nervous system.
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PMID:Failure of brain-derived neurotrophic factor-dependent neuron survival in mouse trisomy 16. 1192 22

Treatment with bone marrow stromal cells (BMSCs) ameliorates neurological functional deficits after stroke. Nerve growth factor (NGF) is a neurotrophic factor that supports the survival and growth of neural cells. Noggin, an antagonist of bone morphogenetic protein (BMP), promotes the differentiation of stem cells into neurons. In this study, we hypothesize that transfection of NGF and Noggin in BMSC treatment of stroke promotes BMSC neuronal differentiation and improves functional outcome after stroke. Adenovirus was used to trasfect NGF and Noggin and the transfection efficiency was measured by Western blot and immunostaining in vitro. The transfected BMSCs with NGF and/or Noggin were administered intravenously at 5 days after middle cerebral artery occlusion (MCAo) in rats. The neurological functional outcome and BMSC migration and differentiation in the ischemic brain were measured. The transplantation of BMSCs with NGF or Noggin elicited neurological functional improvement, promoted BMSCs present in the ischemic brain, and also up-regulated neuro-like cell differentiation as well as increased synaptophysin expression in the ischemic brain compared with nontreatment control animals (P< 0.05). Treatment of stroke with a combination of transfection of NGF and Noggin in BMSCs induced a synergistic effect on improved neurological functional outcome, BMSCs present in the ischemic brain, and synaptophysin expression in the ischemic brain compared with BMSCs transfected with an NGF- or Noggin-alone group (P < 0.05). These data demonstrate that increasing NGF or Noggin expression in BMSCs contributes to brain plasticity after stroke and that a synergistic effect is induced on the coexistence of NGF and Noggin in BMSCs treatment of stroke.
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PMID:Effects of nerve growth factor and Noggin-modified bone marrow stromal cells on stroke in rats. 2116 29

Mutations in the connexin 26 gene (GJB2) are the most common genetic cause of deafness, leading to congenital bilateral non-syndromic sensorineural hearing loss. Here we report the generation of a mouse model for a connexin 26 (Cx26) mutation, in which cre-Sox10 drives excision of the Cx26 gene from non-sensory cells flanking the auditory epithelium. We determined that these conditional knockout mice, designated Gjb2-CKO, have a severe hearing loss. Immunocytochemistry of the auditory epithelium confirmed absence of Cx26 in the non-sensory cells. Histology of the organ of Corti and the spiral ganglion neurons (SGNs) performed at ages 1, 3, or 6 months revealed that in Gjb2-CKO mice, the organ of Corti began to degenerate in the basal cochlear turn at an early stage, and the degeneration rapidly spread to the apex. In addition, the density of SGNs in Rosenthal's canal decreased rapidly along a gradient from the base of the cochlea to the apex, where some SGNs survived until at least 6 months of age. Surviving neurons often clustered together and formed clumps of cells in the canal. We then assessed the influence of brain derived neurotrophic factor (BDNF) gene therapy on the SGNs of Gjb2-CKO mice by inoculating Adenovirus with the BDNF gene insert (Ad.BDNF) into the base of the cochlea via the scala tympani or scala media. We determined that over-expression of BDNF beginning around 1 month of age resulted in a significant rescue of neurons in Rosenthal's canal of the cochlear basal turn but not in the middle or apical portions. This data may be used to design therapies for enhancing the SGN physiological status in all GJB2 patients and especially in a sub-group of GJB2 patients where the hearing loss progresses due to ongoing degeneration of the auditory nerve, thereby improving the outcome of cochlear implant therapy in these ears.
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PMID:Connexin 26 null mice exhibit spiral ganglion degeneration that can be blocked by BDNF gene therapy. 2433 1