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Self-assembling nanofibers alter the processing of amyloid precursor protein in a transgenic mouse model of Alzheimer's disease.
Neurol Res. 2015 Jan; 37(1):84-91.NR

Abstract

BACKGROUND

Alzheimer's disease (AD) is one of the most common dementia, which is not effectively cured to date. Amyloid-beta (Abeta) deposition cascade and disintegrity of brain extracellular matrix (ECM) scaffold attribute to the progress of AD. Thus, it maybe an effective way to treat AD by altering the processing of amyloid precursor protein (APP) and regaining the integrity of ECM. The peptide amphiphile (PA) with a laminin epitope isoleucine-lysine-valine-alanine-valine (IKVAV) (IKVAV-PA) can be trigged into ECM in vivo. In addition, IKVAV-PA could significantly improve cognitive impairment with remarkable increase of endoneurogensis in the hippocampus, as well as reduction of burden of amyloid plaque in the brain.

METHODS

We used heterozygous AbetaPPswe/PS1dE9 double transgenic mice as the animal model of AD. After 1 week of initial stereotaxic administration into bilateral hippocampus, the mice were subjected to the Morris Water Maze (MWM) test. At the end of MWM test, immunohistochemical staining, Western blot and real-time polymerase chain reaction (PCR) were performed in mice.

RESULTS

Here we showed that IKVAV-PA significantly improved cognitive impairment accompanying with reducing the burden of Abeta plaques, as well as the levels of soluble Abeta1-40 and Abeta1-42 in the cortex and hippocampus after 2 weeks of initial administration into bilateral hippocampus. Further examination demonstrated that IKVAV-PA also altered the processing of APP via inhibiting the gene expression of beta-secretase (BACE1), as well as improving the gene expression of insulin-degrading enzyme (IDE) and neprilysin (NEP).

CONCLUSION

Our data suggest that IKVAV-PA may serve as an alternative therapeutic intervention for treating the learning and memory losses in AD.

Authors

No 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

25005263

Citation

Yang, Hongna, et al. "Self-assembling Nanofibers Alter the Processing of Amyloid Precursor Protein in a Transgenic Mouse Model of Alzheimer's Disease." Neurological Research, vol. 37, no. 1, 2015, pp. 84-91.
Yang H, Yang H, Xie Z, et al. Self-assembling nanofibers alter the processing of amyloid precursor protein in a transgenic mouse model of Alzheimer's disease. Neurol Res. 2015;37(1):84-91.
Yang, H., Yang, H., Xie, Z., Wang, P., & Bi, J. (2015). Self-assembling nanofibers alter the processing of amyloid precursor protein in a transgenic mouse model of Alzheimer's disease. Neurological Research, 37(1), 84-91. https://doi.org/10.1179/1743132814Y.0000000417
Yang H, et al. Self-assembling Nanofibers Alter the Processing of Amyloid Precursor Protein in a Transgenic Mouse Model of Alzheimer's Disease. Neurol Res. 2015;37(1):84-91. PubMed PMID: 25005263.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Self-assembling nanofibers alter the processing of amyloid precursor protein in a transgenic mouse model of Alzheimer's disease. AU - Yang,Hongna, AU - Yang,Hongling, AU - Xie,Zhaohong, AU - Wang,Ping, AU - Bi,Jianzhong, Y1 - 2014/07/09/ PY - 2014/7/10/entrez PY - 2014/7/10/pubmed PY - 2015/7/22/medline KW - Alzheimer’s disease, KW - Impaired cognition, KW - Processing of APP KW - Self-assembling nanofibers, SP - 84 EP - 91 JF - Neurological research JO - Neurol. Res. VL - 37 IS - 1 N2 - BACKGROUND: Alzheimer's disease (AD) is one of the most common dementia, which is not effectively cured to date. Amyloid-beta (Abeta) deposition cascade and disintegrity of brain extracellular matrix (ECM) scaffold attribute to the progress of AD. Thus, it maybe an effective way to treat AD by altering the processing of amyloid precursor protein (APP) and regaining the integrity of ECM. The peptide amphiphile (PA) with a laminin epitope isoleucine-lysine-valine-alanine-valine (IKVAV) (IKVAV-PA) can be trigged into ECM in vivo. In addition, IKVAV-PA could significantly improve cognitive impairment with remarkable increase of endoneurogensis in the hippocampus, as well as reduction of burden of amyloid plaque in the brain. METHODS: We used heterozygous AbetaPPswe/PS1dE9 double transgenic mice as the animal model of AD. After 1 week of initial stereotaxic administration into bilateral hippocampus, the mice were subjected to the Morris Water Maze (MWM) test. At the end of MWM test, immunohistochemical staining, Western blot and real-time polymerase chain reaction (PCR) were performed in mice. RESULTS: Here we showed that IKVAV-PA significantly improved cognitive impairment accompanying with reducing the burden of Abeta plaques, as well as the levels of soluble Abeta1-40 and Abeta1-42 in the cortex and hippocampus after 2 weeks of initial administration into bilateral hippocampus. Further examination demonstrated that IKVAV-PA also altered the processing of APP via inhibiting the gene expression of beta-secretase (BACE1), as well as improving the gene expression of insulin-degrading enzyme (IDE) and neprilysin (NEP). CONCLUSION: Our data suggest that IKVAV-PA may serve as an alternative therapeutic intervention for treating the learning and memory losses in AD. SN - 1743-1328 UR - https://www.unboundmedicine.com/medline/citation/25005263/Self_assembling_nanofibers_alter_the_processing_of_amyloid_precursor_protein_in_a_transgenic_mouse_model_of_Alzheimer's_disease_ L2 - http://www.tandfonline.com/doi/full/10.1179/1743132814Y.0000000417 DB - PRIME DP - Unbound Medicine ER -