Aminostyrylbenzofuran directly reduces oligomeric amyloid-β and reverses cognitive deficits in Alzheimer transgenic mice.

Alzheimer's disease is an irreversible neurodegenerative disorder that is characterized by the abnormal aggregation of amyloid-β into neurotoxic oligomers and plaques. Although many disease-modifying molecules are currently in Alzheimer clinical trials, a small molecule that inhibits amyloid-β...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sang-Hyun Lee, YoungSoo Kim, Hye Yun Kim, Young Hoon Kim, Maeng Sup Kim, Jae Yang Kong, Mun-Han Lee, Dong Jin Kim, Young Gil Ahn
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/71619b57b0bf44738486e164ad55a88f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:71619b57b0bf44738486e164ad55a88f
record_format	dspace
spelling	oai:doaj.org-article:71619b57b0bf44738486e164ad55a88f2021-11-18T08:21:41ZAminostyrylbenzofuran directly reduces oligomeric amyloid-β and reverses cognitive deficits in Alzheimer transgenic mice.1932-620310.1371/journal.pone.0095733https://doaj.org/article/71619b57b0bf44738486e164ad55a88f2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24760018/?tool=EBIhttps://doaj.org/toc/1932-6203Alzheimer's disease is an irreversible neurodegenerative disorder that is characterized by the abnormal aggregation of amyloid-β into neurotoxic oligomers and plaques. Although many disease-modifying molecules are currently in Alzheimer clinical trials, a small molecule that inhibits amyloid-β aggregation and ameliorates the disorder has not been approved to date. Herein, we report the effects of a potent small molecule, 6-methoxy-2-(4-dimethylaminostyryl) benzofuran (KMS88009), that directly disrupts amyloid-β oligomerization, preserving cognitive behavior when used prophylactically and reversing declines in cognitive behavior when used therapeutically. KMS88009 exhibited excellent pharmacokinetic profiles with extensive brain uptake and a high level of safety. When orally administered before and after the onset of Alzheimer's disease symptoms, KMS88009 significantly reduced assembly of amyloid-β oligomers and improved cognitive behaviors in the APP/PS1 double transgenic mouse model. The unique dual mode of action indicates that KMS88009 may be a powerful therapeutic candidate for the treatment of Alzheimer's disease.Sang-Hyun LeeYoungSoo KimHye Yun KimYoung Hoon KimMaeng Sup KimJae Yang KongMun-Han LeeDong Jin KimYoung Gil AhnPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e95733 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sang-Hyun Lee YoungSoo Kim Hye Yun Kim Young Hoon Kim Maeng Sup Kim Jae Yang Kong Mun-Han Lee Dong Jin Kim Young Gil Ahn Aminostyrylbenzofuran directly reduces oligomeric amyloid-β and reverses cognitive deficits in Alzheimer transgenic mice.
description	Alzheimer's disease is an irreversible neurodegenerative disorder that is characterized by the abnormal aggregation of amyloid-β into neurotoxic oligomers and plaques. Although many disease-modifying molecules are currently in Alzheimer clinical trials, a small molecule that inhibits amyloid-β aggregation and ameliorates the disorder has not been approved to date. Herein, we report the effects of a potent small molecule, 6-methoxy-2-(4-dimethylaminostyryl) benzofuran (KMS88009), that directly disrupts amyloid-β oligomerization, preserving cognitive behavior when used prophylactically and reversing declines in cognitive behavior when used therapeutically. KMS88009 exhibited excellent pharmacokinetic profiles with extensive brain uptake and a high level of safety. When orally administered before and after the onset of Alzheimer's disease symptoms, KMS88009 significantly reduced assembly of amyloid-β oligomers and improved cognitive behaviors in the APP/PS1 double transgenic mouse model. The unique dual mode of action indicates that KMS88009 may be a powerful therapeutic candidate for the treatment of Alzheimer's disease.
format	article
author	Sang-Hyun Lee YoungSoo Kim Hye Yun Kim Young Hoon Kim Maeng Sup Kim Jae Yang Kong Mun-Han Lee Dong Jin Kim Young Gil Ahn
author_facet	Sang-Hyun Lee YoungSoo Kim Hye Yun Kim Young Hoon Kim Maeng Sup Kim Jae Yang Kong Mun-Han Lee Dong Jin Kim Young Gil Ahn
author_sort	Sang-Hyun Lee
title	Aminostyrylbenzofuran directly reduces oligomeric amyloid-β and reverses cognitive deficits in Alzheimer transgenic mice.
title_short	Aminostyrylbenzofuran directly reduces oligomeric amyloid-β and reverses cognitive deficits in Alzheimer transgenic mice.
title_full	Aminostyrylbenzofuran directly reduces oligomeric amyloid-β and reverses cognitive deficits in Alzheimer transgenic mice.
title_fullStr	Aminostyrylbenzofuran directly reduces oligomeric amyloid-β and reverses cognitive deficits in Alzheimer transgenic mice.
title_full_unstemmed	Aminostyrylbenzofuran directly reduces oligomeric amyloid-β and reverses cognitive deficits in Alzheimer transgenic mice.
title_sort	aminostyrylbenzofuran directly reduces oligomeric amyloid-β and reverses cognitive deficits in alzheimer transgenic mice.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/71619b57b0bf44738486e164ad55a88f
work_keys_str_mv	AT sanghyunlee aminostyrylbenzofurandirectlyreducesoligomericamyloidbandreversescognitivedeficitsinalzheimertransgenicmice AT youngsookim aminostyrylbenzofurandirectlyreducesoligomericamyloidbandreversescognitivedeficitsinalzheimertransgenicmice AT hyeyunkim aminostyrylbenzofurandirectlyreducesoligomericamyloidbandreversescognitivedeficitsinalzheimertransgenicmice AT younghoonkim aminostyrylbenzofurandirectlyreducesoligomericamyloidbandreversescognitivedeficitsinalzheimertransgenicmice AT maengsupkim aminostyrylbenzofurandirectlyreducesoligomericamyloidbandreversescognitivedeficitsinalzheimertransgenicmice AT jaeyangkong aminostyrylbenzofurandirectlyreducesoligomericamyloidbandreversescognitivedeficitsinalzheimertransgenicmice AT munhanlee aminostyrylbenzofurandirectlyreducesoligomericamyloidbandreversescognitivedeficitsinalzheimertransgenicmice AT dongjinkim aminostyrylbenzofurandirectlyreducesoligomericamyloidbandreversescognitivedeficitsinalzheimertransgenicmice AT younggilahn aminostyrylbenzofurandirectlyreducesoligomericamyloidbandreversescognitivedeficitsinalzheimertransgenicmice
_version_	1718421865640230912

Aminostyrylbenzofuran directly reduces oligomeric amyloid-β and reverses cognitive deficits in Alzheimer transgenic mice.

Ejemplares similares