K114 Inhibits A-beta Aggregation and Inflammation In Vitro and In Vivo in AD/Tg Mice

ISSN: 1875-5828 (Online)
ISSN: 1567-2050 (Print)


Volume 11, 10 Issues, 2014


Download PDF Flyer




Current Alzheimer Research

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 38th of 194 in Clinical Neurology
  • 80th of 251 in Neurosciences

Submit Abstracts Online Submit Manuscripts Online

Editor-in-Chief:
Prof. Debomoy K. Lahiri
Department of Psychiatry, Indiana University School of Medicine
Neuroscience Research Center
Indianapolis, IN 46202
USA


View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 3.796
5 - Year: 3.998

K114 Inhibits A-beta Aggregation and Inflammation In Vitro and In Vivo in AD/Tg Mice

Author(s): Yi-Hong Zhang, Dushyant Mann, James Raymick, Sumit Sarkar, Merle G. Paule, Debomoy K. Lahiri, Melanie Dumas, Ashlee Bell- Cohen and Larry C. Schmued

Affiliation: Division of Neurotoxicology, National Center for Toxicological Research (NCTR)/FDA, Jefferson, AR 72079, USA.

Abstract

Alzheimer’s disease (AD) is the most common age related human neurodegenerative disorder. The major histopathological characteristics of the AD brain are extracellular amyloid-beta (Aβ ) peptide loaded plaques and intraneuronal neurofibrillary tangles made of phosphorylated tau proteins. Amyloid plaques consist primarily of aggregated A β 1-42 and Aβ 1-40 peptides. The aim of our current study was to test novel ligands/agents with the potential to disrupt or inhibit the aggregation of Aβ peptide, specifically K114, (trans,trans)-1-bromo-2,5-bis(4-hydroxystyryl)benzene, which was initially developed as a potential positron emission tomography (PET) ligand for the in vivo detection of amyloid plaques. Systemic administration of K114 has been shown in the AD/transgenic (Tg) mouse model to be capable of crossing the blood-brain barrier (BBB) and be colocalized with amyloid plaques. In this study we determined whether K114 has the potential to inhibit Aβ aggregation in vitro in AD/Tg mice and also tested, in vivo, whether chronic daily orally administered K114 has any therapeutic potential as evidenced by inhibition or reduction of the deposits of amyloid aggregates in the brains of AD/Tg mice. Our results demonstrated that K114 strongly blocked, in vitro, the aggregation of A β peptide in the amyloid plaques of AD/Tg mouse brain. Systemic treatment with K114 was also effective in significantly reducing the deposits of amyloid plaques in the brains of living transgenic AD mice. Additionally, K114 significantly inhibited the typically observed plaque associated astrocytic activation, as revealed by GFAP immunohistochemistry, suggesting possible anti-inflammatory properties.

Keywords: Alzheimer’s disease, amyloid- β aggregation, amyloid plaques, astrocytes, K114.

Purchase Online Rights and Permissions

  
  



Article Details

Volume: 11
Issue Number: 3
First Page: 299
Last Page: 308
Page Count: 10
DOI: 10.2174/1567205011666140220125324
Advertisement

Related Journals




Webmaster Contact: urooj@benthamscience.org Copyright © 2014 Bentham Science