Intracranial injection of AAV expressing NEP but not IDE reduces amyloid pathology in APP+PS1 transgenic mice.

The accumulation of β-amyloid peptides in the brain has been recognized as an essential factor in Alzheimer's disease pathology. Several proteases, including Neprilysin (NEP), endothelin converting enzyme (ECE), and insulin degrading enzyme (IDE), have been shown to cleave β-amyloid peptides (A...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Nikisha Carty, Kevin R Nash, Milene Brownlow, Dana Cruite, Donna Wilcock, Maj-Linda B Selenica, Daniel C Lee, Marcia N Gordon, Dave Morgan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c61b562f15eb4169a63bb0f3b5b93a3e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c61b562f15eb4169a63bb0f3b5b93a3e
record_format	dspace
spelling	oai:doaj.org-article:c61b562f15eb4169a63bb0f3b5b93a3e2021-11-18T07:51:36ZIntracranial injection of AAV expressing NEP but not IDE reduces amyloid pathology in APP+PS1 transgenic mice.1932-620310.1371/journal.pone.0059626https://doaj.org/article/c61b562f15eb4169a63bb0f3b5b93a3e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555730/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The accumulation of β-amyloid peptides in the brain has been recognized as an essential factor in Alzheimer's disease pathology. Several proteases, including Neprilysin (NEP), endothelin converting enzyme (ECE), and insulin degrading enzyme (IDE), have been shown to cleave β-amyloid peptides (Aβ). We have previously reported reductions in amyloid in APP+PS1 mice with increased expression of ECE. In this study we compared the vector-induced increased expression of NEP and IDE. We used recombinant adeno-associated viral vectors expressing either native forms of NEP (NEP-n) or IDE (IDE-n), or engineered secreted forms of NEP (NEP-s) or IDE (IDE-s). In a six-week study, immunohistochemistry staining for total Aβ was significantly decreased in animals receiving the NEP-n and NEP-s but not for IDE-n or IDE-s in either the hippocampus or cortex. Congo red staining followed a similar trend revealing significant decreases in the hippocampus and the cortex for NEP-n and NEP-s treatment groups. Our results indicate that while rAAV-IDE does not have the same therapeutic potential as rAAV-NEP, rAAV-NEP-s and NEP-n are effective at reducing amyloid loads, and both of these vectors continue to have significant effects nine months post-injection. As such, they may be considered reasonable candidates for gene therapy trials in AD.Nikisha CartyKevin R NashMilene BrownlowDana CruiteDonna WilcockMaj-Linda B SelenicaDaniel C LeeMarcia N GordonDave MorganPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e59626 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nikisha Carty Kevin R Nash Milene Brownlow Dana Cruite Donna Wilcock Maj-Linda B Selenica Daniel C Lee Marcia N Gordon Dave Morgan Intracranial injection of AAV expressing NEP but not IDE reduces amyloid pathology in APP+PS1 transgenic mice.
description	The accumulation of β-amyloid peptides in the brain has been recognized as an essential factor in Alzheimer's disease pathology. Several proteases, including Neprilysin (NEP), endothelin converting enzyme (ECE), and insulin degrading enzyme (IDE), have been shown to cleave β-amyloid peptides (Aβ). We have previously reported reductions in amyloid in APP+PS1 mice with increased expression of ECE. In this study we compared the vector-induced increased expression of NEP and IDE. We used recombinant adeno-associated viral vectors expressing either native forms of NEP (NEP-n) or IDE (IDE-n), or engineered secreted forms of NEP (NEP-s) or IDE (IDE-s). In a six-week study, immunohistochemistry staining for total Aβ was significantly decreased in animals receiving the NEP-n and NEP-s but not for IDE-n or IDE-s in either the hippocampus or cortex. Congo red staining followed a similar trend revealing significant decreases in the hippocampus and the cortex for NEP-n and NEP-s treatment groups. Our results indicate that while rAAV-IDE does not have the same therapeutic potential as rAAV-NEP, rAAV-NEP-s and NEP-n are effective at reducing amyloid loads, and both of these vectors continue to have significant effects nine months post-injection. As such, they may be considered reasonable candidates for gene therapy trials in AD.
format	article
author	Nikisha Carty Kevin R Nash Milene Brownlow Dana Cruite Donna Wilcock Maj-Linda B Selenica Daniel C Lee Marcia N Gordon Dave Morgan
author_facet	Nikisha Carty Kevin R Nash Milene Brownlow Dana Cruite Donna Wilcock Maj-Linda B Selenica Daniel C Lee Marcia N Gordon Dave Morgan
author_sort	Nikisha Carty
title	Intracranial injection of AAV expressing NEP but not IDE reduces amyloid pathology in APP+PS1 transgenic mice.
title_short	Intracranial injection of AAV expressing NEP but not IDE reduces amyloid pathology in APP+PS1 transgenic mice.
title_full	Intracranial injection of AAV expressing NEP but not IDE reduces amyloid pathology in APP+PS1 transgenic mice.
title_fullStr	Intracranial injection of AAV expressing NEP but not IDE reduces amyloid pathology in APP+PS1 transgenic mice.
title_full_unstemmed	Intracranial injection of AAV expressing NEP but not IDE reduces amyloid pathology in APP+PS1 transgenic mice.
title_sort	intracranial injection of aav expressing nep but not ide reduces amyloid pathology in app+ps1 transgenic mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c61b562f15eb4169a63bb0f3b5b93a3e
work_keys_str_mv	AT nikishacarty intracranialinjectionofaavexpressingnepbutnotidereducesamyloidpathologyinappps1transgenicmice AT kevinrnash intracranialinjectionofaavexpressingnepbutnotidereducesamyloidpathologyinappps1transgenicmice AT milenebrownlow intracranialinjectionofaavexpressingnepbutnotidereducesamyloidpathologyinappps1transgenicmice AT danacruite intracranialinjectionofaavexpressingnepbutnotidereducesamyloidpathologyinappps1transgenicmice AT donnawilcock intracranialinjectionofaavexpressingnepbutnotidereducesamyloidpathologyinappps1transgenicmice AT majlindabselenica intracranialinjectionofaavexpressingnepbutnotidereducesamyloidpathologyinappps1transgenicmice AT danielclee intracranialinjectionofaavexpressingnepbutnotidereducesamyloidpathologyinappps1transgenicmice AT marciangordon intracranialinjectionofaavexpressingnepbutnotidereducesamyloidpathologyinappps1transgenicmice AT davemorgan intracranialinjectionofaavexpressingnepbutnotidereducesamyloidpathologyinappps1transgenicmice
_version_	1718422880106053632

Intracranial injection of AAV expressing NEP but not IDE reduces amyloid pathology in APP+PS1 transgenic mice.

Ejemplares similares