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Lab News

03-02-15 Joe wins 2015 New Vision Award
Joe had a very successful conference last week, and was awarded the 2015 New Vision Award at the Charleston Conference on Alzheimer’s disease. This is a highly selective award (with money!) which involves a first round of selections to attend the conference and then a study section-like discussion of the remaining entries at the conference. Joe’s proposal was selected unanimously.
01-27-15 Tony speaks at World Economic Forum
Tony was invited to Davos to discuss how to tackle brain diseases at the World Economic Forum!
12-02-14 Final round for Breakthrough of the Year!
We made the final round for Science's 2014 Breakthrough of the year!  Let everyone know so they can vote!
11-13-14 Vote for the breakthrough of the year!
Help us win Sciene Breakthrough of 2014 by voting for "Young blood fixes old."
09-23-14 Creative Minds: Tony and Tom are in the news!
Congratulations to Tony and Tom for being in the NIH Director's blog.  You can read it here!

pubmed: wyss-coray

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    Small molecule p75NTR ligands reduce pathological phosphorylation and misfolding of tau, inflammatory changes, cholinergic degeneration, and cognitive deficits in AβPP(L/S) transgenic mice.

    J Alzheimers Dis. 2014;42(2):459-83

    Authors: Nguyen TV, Shen L, Vander Griend L, Quach LN, Belichenko NP, Saw N, Yang T, Shamloo M, Wyss-Coray T, Massa SM, Longo FM

    Abstract
    The p75 neurotrophin receptor (p75NTR) is involved in degenerative mechanisms related to Alzheimer's disease (AD). In addition, p75NTR levels are increased in AD and the receptor is expressed by neurons that are particularly vulnerable in the disease. Therefore, modulating p75NTR function may be a significant disease-modifying treatment approach. Prior studies indicated that the non-peptide, small molecule p75NTR ligands LM11A-31, and chemically unrelated LM11A-24, could block amyloid-β-induced deleterious signaling and neurodegeneration in vitro, and LM11A-31 was found to mitigate neuritic degeneration and behavioral deficits in a mouse model of AD. In this study, we determined whether these in vivo findings represent class effects of p75NTR ligands by examining LM11A-24 effects. In addition, the range of compound effects was further examined by evaluating tau pathology and neuroinflammation. Following oral administration, both ligands reached brain concentrations known to provide neuroprotection in vitro. Compound induction of p75NTR cleavage provided evidence for CNS target engagement. LM11A-31 and LM11A-24 reduced excessive phosphorylation of tau, and LM11A-31 also inhibited its aberrant folding. Both ligands decreased activation of microglia, while LM11A-31 attenuated reactive astrocytes. Along with decreased inflammatory responses, both ligands reduced cholinergic neurite degeneration. In addition to the amelioration of neuropathology in AD model mice, LM11A-31, but not LM11A-24, prevented impairments in water maze performance, while both ligands prevented deficits in fear conditioning. These findings support a role for p75NTR ligands in preventing fundamental tau-related pathologic mechanisms in AD, and further validate the development of these small molecules as a new class of therapeutic compounds.

    PMID: 24898660 [PubMed - indexed for MEDLINE]