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NPT088 reduces both amyloid-β and tau pathologies in transgenic mice
INTRODUCTION: Alzheimer's disease (AD) is characterized by appearance of both extracellular senile plaques and intracellular neurofibrillary tangles, comprised of aggregates of misfolded amyloid-β (Aβ) and hyper-phosphorylated tau, respectively. In a previous study, we demonstrated that g3p, a...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651359/ https://www.ncbi.nlm.nih.gov/pubmed/29067301 http://dx.doi.org/10.1016/j.trci.2016.06.004 |
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author | Levenson, Jonathan M. Schroeter, Sally Carroll, Jenna C. Cullen, Valerie Asp, Eva Proschitsky, Ming Chung, Charlotte H.-Y. Gilead, Sharon Nadeem, Muhammad Dodiya, Hemraj B. Shoaga, Shadiyat Mufson, Elliott J. Tsubery, Haim Krishnan, Rajaraman Wright, Jason Solomon, Beka Fisher, Richard Gannon, Kimberley S. |
author_facet | Levenson, Jonathan M. Schroeter, Sally Carroll, Jenna C. Cullen, Valerie Asp, Eva Proschitsky, Ming Chung, Charlotte H.-Y. Gilead, Sharon Nadeem, Muhammad Dodiya, Hemraj B. Shoaga, Shadiyat Mufson, Elliott J. Tsubery, Haim Krishnan, Rajaraman Wright, Jason Solomon, Beka Fisher, Richard Gannon, Kimberley S. |
author_sort | Levenson, Jonathan M. |
collection | PubMed |
description | INTRODUCTION: Alzheimer's disease (AD) is characterized by appearance of both extracellular senile plaques and intracellular neurofibrillary tangles, comprised of aggregates of misfolded amyloid-β (Aβ) and hyper-phosphorylated tau, respectively. In a previous study, we demonstrated that g3p, a capsid protein from bacteriophage M13, binds to and remodels misfolded aggregates of proteins that assume an amyloid conformation. We engineered a fusion protein (“NPT088”) consisting of the active fragment of g3p and human-IgG(1)-Fc. METHODS: Aged Tg2576 mice or rTg4510 mice received NPT088 weekly via IP injection. Cognitive and/or functional motor endpoints were monitored during dosing. Pathology was quantified biochemically and immunohistochemically. RESULTS: NPT088-lowered Aβ plaque and improved cognitive performance of aged Tg2576 mice. Moreover, NPT088 reduced phospho-tau pathology, reduced brain atrophy, and improved cognition in rTg4510 mice. DISCUSSION: These observations establish NPT088 as a novel therapeutic approach and potential drug class that targets both Aβ and tau, the hallmark pathologies of AD. |
format | Online Article Text |
id | pubmed-5651359 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-56513592017-10-24 NPT088 reduces both amyloid-β and tau pathologies in transgenic mice Levenson, Jonathan M. Schroeter, Sally Carroll, Jenna C. Cullen, Valerie Asp, Eva Proschitsky, Ming Chung, Charlotte H.-Y. Gilead, Sharon Nadeem, Muhammad Dodiya, Hemraj B. Shoaga, Shadiyat Mufson, Elliott J. Tsubery, Haim Krishnan, Rajaraman Wright, Jason Solomon, Beka Fisher, Richard Gannon, Kimberley S. Alzheimers Dement (N Y) Featured Article INTRODUCTION: Alzheimer's disease (AD) is characterized by appearance of both extracellular senile plaques and intracellular neurofibrillary tangles, comprised of aggregates of misfolded amyloid-β (Aβ) and hyper-phosphorylated tau, respectively. In a previous study, we demonstrated that g3p, a capsid protein from bacteriophage M13, binds to and remodels misfolded aggregates of proteins that assume an amyloid conformation. We engineered a fusion protein (“NPT088”) consisting of the active fragment of g3p and human-IgG(1)-Fc. METHODS: Aged Tg2576 mice or rTg4510 mice received NPT088 weekly via IP injection. Cognitive and/or functional motor endpoints were monitored during dosing. Pathology was quantified biochemically and immunohistochemically. RESULTS: NPT088-lowered Aβ plaque and improved cognitive performance of aged Tg2576 mice. Moreover, NPT088 reduced phospho-tau pathology, reduced brain atrophy, and improved cognition in rTg4510 mice. DISCUSSION: These observations establish NPT088 as a novel therapeutic approach and potential drug class that targets both Aβ and tau, the hallmark pathologies of AD. Elsevier 2016-07-14 /pmc/articles/PMC5651359/ /pubmed/29067301 http://dx.doi.org/10.1016/j.trci.2016.06.004 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Featured Article Levenson, Jonathan M. Schroeter, Sally Carroll, Jenna C. Cullen, Valerie Asp, Eva Proschitsky, Ming Chung, Charlotte H.-Y. Gilead, Sharon Nadeem, Muhammad Dodiya, Hemraj B. Shoaga, Shadiyat Mufson, Elliott J. Tsubery, Haim Krishnan, Rajaraman Wright, Jason Solomon, Beka Fisher, Richard Gannon, Kimberley S. NPT088 reduces both amyloid-β and tau pathologies in transgenic mice |
title | NPT088 reduces both amyloid-β and tau pathologies in transgenic mice |
title_full | NPT088 reduces both amyloid-β and tau pathologies in transgenic mice |
title_fullStr | NPT088 reduces both amyloid-β and tau pathologies in transgenic mice |
title_full_unstemmed | NPT088 reduces both amyloid-β and tau pathologies in transgenic mice |
title_short | NPT088 reduces both amyloid-β and tau pathologies in transgenic mice |
title_sort | npt088 reduces both amyloid-β and tau pathologies in transgenic mice |
topic | Featured Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651359/ https://www.ncbi.nlm.nih.gov/pubmed/29067301 http://dx.doi.org/10.1016/j.trci.2016.06.004 |
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