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Expression of the plant viral protease NIa in the brain of a mouse model of Alzheimer's disease mitigates Aβ pathology and improves cognitive function.
Exp Mol Med. 2012 Dec 31; 44(12):740-8.EM

Abstract

The plant viral protease, NIa, has a strict substrate specificity for the consensus sequence of Val-Xaa-His-Gln, with a scissoring property after Gln. We recently reported that NIa efficiently cleaved the amyloid-β (Aβ) peptide, which contains the sequence Val-His-His-Gln in the vicinity of the cleavage site by α-secretase, and that the expression of NIa using a lentiviral system in the brain of AD mouse model reduced plaque deposition levels. In the present study, we investigated whether exogenous expression of NIa in the brain of AD mouse model is beneficial to the improvement of cognitive deficits. To address this question, Lenti-NIa was intracerebrally injected into the brain of Tg-APPswe/ PS1dE9 (Tg-APP/PS1) mice at 7 months of age and behavioral tests were performed 15-30 days afterwards. The results of the water maze test indicated that Tg-APP/PS1 mice which had been injected with Lenti-GFP showed an increased latency in finding the hidden-platform and markedly enhanced navigation near the maze-wall, and that such behavioral deficits were significantly reversed in Tg-APP/PS1 mice injected with Lenti-NIa. In the passive avoidance test, Tg-APP/PS1 mice exhibited a severe deficit in their contextual memory retention, which was reversed by NIa expression. In the marble burying test, Tg-APP/PS1 mice buried marbles fewer than non-transgenic mice, which was also significantly improved by NIa. After behavioral tests, it was verified that the Tg-APP/PS1 mice with Lenti-NIa injection had reduced Aβ levels and plaque deposition when compared to Tg-APP/PS1 mice. These results showed that the plant viral protease, NIa, not only reduces Aβ pathology, but also improves behavioral deficits.

Authors+Show Affiliations

Department of Brain and Cognitive Sciences, Ewha Womans University Seoul 120-750, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23172351

Citation

Kim, Tae-Kyung, et al. "Expression of the Plant Viral Protease NIa in the Brain of a Mouse Model of Alzheimer's Disease Mitigates Aβ Pathology and Improves Cognitive Function." Experimental & Molecular Medicine, vol. 44, no. 12, 2012, pp. 740-8.
Kim TK, Han HE, Kim H, et al. Expression of the plant viral protease NIa in the brain of a mouse model of Alzheimer's disease mitigates Aβ pathology and improves cognitive function. Exp Mol Med. 2012;44(12):740-8.
Kim, T. K., Han, H. E., Kim, H., Lee, J. E., Choi, D., Park, W. J., & Han, P. L. (2012). Expression of the plant viral protease NIa in the brain of a mouse model of Alzheimer's disease mitigates Aβ pathology and improves cognitive function. Experimental & Molecular Medicine, 44(12), 740-8. https://doi.org/10.3858/emm.2012.44.12.082
Kim TK, et al. Expression of the Plant Viral Protease NIa in the Brain of a Mouse Model of Alzheimer's Disease Mitigates Aβ Pathology and Improves Cognitive Function. Exp Mol Med. 2012 Dec 31;44(12):740-8. PubMed PMID: 23172351.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of the plant viral protease NIa in the brain of a mouse model of Alzheimer's disease mitigates Aβ pathology and improves cognitive function. AU - Kim,Tae-Kyung, AU - Han,Hye-Eun, AU - Kim,Hannah, AU - Lee,Jung-Eun, AU - Choi,Daehan, AU - Park,Woo Jin, AU - Han,Pyung-Lim, PY - 2012/11/23/entrez PY - 2012/11/23/pubmed PY - 2013/5/22/medline SP - 740 EP - 8 JF - Experimental & molecular medicine JO - Exp. Mol. Med. VL - 44 IS - 12 N2 - The plant viral protease, NIa, has a strict substrate specificity for the consensus sequence of Val-Xaa-His-Gln, with a scissoring property after Gln. We recently reported that NIa efficiently cleaved the amyloid-β (Aβ) peptide, which contains the sequence Val-His-His-Gln in the vicinity of the cleavage site by α-secretase, and that the expression of NIa using a lentiviral system in the brain of AD mouse model reduced plaque deposition levels. In the present study, we investigated whether exogenous expression of NIa in the brain of AD mouse model is beneficial to the improvement of cognitive deficits. To address this question, Lenti-NIa was intracerebrally injected into the brain of Tg-APPswe/ PS1dE9 (Tg-APP/PS1) mice at 7 months of age and behavioral tests were performed 15-30 days afterwards. The results of the water maze test indicated that Tg-APP/PS1 mice which had been injected with Lenti-GFP showed an increased latency in finding the hidden-platform and markedly enhanced navigation near the maze-wall, and that such behavioral deficits were significantly reversed in Tg-APP/PS1 mice injected with Lenti-NIa. In the passive avoidance test, Tg-APP/PS1 mice exhibited a severe deficit in their contextual memory retention, which was reversed by NIa expression. In the marble burying test, Tg-APP/PS1 mice buried marbles fewer than non-transgenic mice, which was also significantly improved by NIa. After behavioral tests, it was verified that the Tg-APP/PS1 mice with Lenti-NIa injection had reduced Aβ levels and plaque deposition when compared to Tg-APP/PS1 mice. These results showed that the plant viral protease, NIa, not only reduces Aβ pathology, but also improves behavioral deficits. SN - 2092-6413 UR - https://www.unboundmedicine.com/medline/citation/23172351/Expression_of_the_plant_viral_protease_NIa_in_the_brain_of_a_mouse_model_of_Alzheimer's_disease_mitigates_Aβ_pathology_and_improves_cognitive_function_ L2 - http://dx.doi.org/10.3858/emm.2012.44.12.082 DB - PRIME DP - Unbound Medicine ER -