AAV2-mediated striatum delivery of human CDNF prevents the deterioration of midbrain dopamine neurons in a 6-hydroxydopamine induced parkinsonian rat model

Ren, Xinmiao; Zhang, Ting; Gong, Xia; Hu, Guanzheng; Ding, Wei; Wang, Xiaomin

doi:10.1016/j.expneurol.2013.06.002

Cited by 87 publications

(60 citation statements)

References 42 publications

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“…2D). The 3 10 helix that spans residues 95-102 (green shaded box in Fig. 2A) has a higher degree of flexibility and is therefore underrepresented among the CDNF conformers (present in 8 out 20 conformers).…”

Section: Three-dimensional Structure Of Full-length Cdnf (Fl-cdnf) Inmentioning

confidence: 99%

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The Solution Structure and Dynamics of Full-length Human Cerebral Dopamine Neurotrophic Factor and Its Neuroprotective Role against α-Synuclein Oligomers

Latge

Cabral

Oliveira

et al. 2015

Journal of Biological Chemistry

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Background: Cerebral dopamine neurotrophic factor (CDNF) is a promising therapeutic agent for treating Parkinson disease. Results: We determined the solution structure of CDNF and demonstrated its neuroprotective effects against insults caused by ␣-synuclein oligomers. Conclusion:We identified structural features of CDNF that might correspond with its physiological activity. Significance: This work strengthens the therapeutic relevance of using CDNF to treat neurodegenerative diseases.

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Section: Three-dimensional Structure Of Full-length Cdnf (Fl-cdnf) Inmentioning

confidence: 99%

“…3). Parkash and co-workers (14) previously reported an x-ray structure corresponding to the N-terminal domain of human CDNF (residues 1-107; PDB code 2W50), which indicated the presence of five ␣-helixes (␣1-␣5) and a 3 10 helix.…”

Section: Key Structural Elements Identified By the Comparison Of Cdnfmentioning

confidence: 99%

The Solution Structure and Dynamics of Full-length Human Cerebral Dopamine Neurotrophic Factor and Its Neuroprotective Role against α-Synuclein Oligomers

Latge

Cabral

Oliveira

et al. 2015

Journal of Biological Chemistry

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“…The primer sequences for BMP-7 were 5'-GTGGACCTCATGGCCTACATG-3' (sense) and 5'-TCAGCAACTGAGGGCCTCTC-3' (antisense). AAV2 vectors were prepared as previously described 18) . Briefly, BHK-21 cells were transfected with the pSNAV-BMP-7 vector using Metafectene and were selected by G418.…”

Section: Cell Culturementioning

confidence: 99%

Dental pulp cells that express adeno-associated virus serotype 2-mediated BMP-7 gene enhanced odontoblastic differentiation

et al. 2014

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This present study investigated the potential of adeno-associated virus serotype 2 (AAV2) mediated BMP-7 (AAV2-BMP-7) to induce odontoblastic differentiation of human dental pulp cells (DPCs) in vitro. AAV2-BMP-7 was constructed to overexpress BMP-7, and the biologic effects of BMP-7 on DPCs were investigated by the evaluation of the activity of alkaline phosphatase (ALPase), the detection of the expression of dentin sialophosphoprotein (DSPP) and osteocalcin (OCN) expression and the analysis of the proliferative ability of the cells. DPCs that were infected with AAV2-BMP-7 displayed significantly upregulated ALP activity and formed mineralized nodules. Moreover, AAV2-BMP-7 promoted the expression of mineralization-related genes, which included DSPP and OCN. In addition, there was no significant difference between the proliferative ability of AAV2-BMP-7 and the control group. In conclusion, AAV2-BMP-7 promoted the odontoblastic differentiation in DPCs, a clear indication of the therapeutic potential of AAV2-BMP-7 in dental tissue regeneration.

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“…Although the etiology of PD is poorly understood and therefore cannot guide the development of knowledge-based targeted therapeutics, investigators have attempted to develop targeted therapies using viral vector technologies to transfer specific genes to neurons, with the aim of improving the function of the degenerating DA system (5,6). Striatal delivery of adeno-associated virus (AAV) 2-mediated cerebral dopamine neurotrophic factor produced neuroprotective and functional restorative effects in the 6-hydroxydopamine (6-OHDA)-induced animal model of PD (7). In addition, our previous studies (8,9) demonstrated that AAV1 transduction with a gene encoding the constitutively active form of ras homolog enriched in the brain, with a mutation of the serine to histidine at the 16 position [Rheb(S16H)], induced trophic effects.…”

Section: Introductionmentioning

confidence: 99%

Roles of Rheb(S16H) in substantia nigra pars compacta dopaminergic neurons in vivo

Jeon

Kim

2014

Biomedical Reports

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Abstract. Although there are ongoing intensive research efforts, no effective pharmacological therapies for Parkinson's disease (PD) have been developed thus far. However, with the development of efficient gene delivery systems, gene therapy for PD has become a focus of research and increasing evidence suggests that continuous production of neurotrophic factors play a significant role in the functional restoration of the nigrostriatal dopaminergic (DA) system. Our recent study reported that the transduction of DA neurons with ras homolog enriched in brain, which has an S16H mutation [Rheb(S16H)], protected the nigrostriatal DA projection in a neurotoxin model of PD in vivo. In addition, Rheb(S16H) expression significantly increased the levels of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor, which contributed to the neuroprotective effects of Rheb(S16H) in DA neurons in the adult brain, indicating that the activation of the signaling pathways involved in cell survival by a specific gene delivery, such as Rheb(S16H) to adult neurons, may be a useful strategy to protect neural systems in the adult brain. In the present study, a brief overview of our recent studies is provided, which demonstrates the neuroprotective mechanisms of Rheb(S16H) on the nigrostriatal DA projection in the adult brain.

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AAV2-mediated striatum delivery of human CDNF prevents the deterioration of midbrain dopamine neurons in a 6-hydroxydopamine induced parkinsonian rat model

Cited by 87 publications

References 42 publications

The Solution Structure and Dynamics of Full-length Human Cerebral Dopamine Neurotrophic Factor and Its Neuroprotective Role against α-Synuclein Oligomers

The Solution Structure and Dynamics of Full-length Human Cerebral Dopamine Neurotrophic Factor and Its Neuroprotective Role against α-Synuclein Oligomers

Dental pulp cells that express adeno-associated virus serotype 2-mediated BMP-7 gene enhanced odontoblastic differentiation

Roles of Rheb(S16H) in substantia nigra pars compacta dopaminergic neurons in vivo

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