کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6807214 1433580 2013 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A small molecule p75NTR ligand prevents cognitive deficits and neurite degeneration in an Alzheimer's mouse model
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
A small molecule p75NTR ligand prevents cognitive deficits and neurite degeneration in an Alzheimer's mouse model
چکیده انگلیسی
The p75 neurotrophin receptor (p75NTR) is associated with multiple mechanisms linked to Alzheimer's disease (AD); hence, modulating its function might confer therapeutic effects. In previous in vitro work, we developed small molecule p75NTR ligands that inhibited amyloid-β-induced degenerative signaling and prevented neurite degeneration. In the present study, a prototype p75NTR ligand, LM11A-31, was administered orally to the Thy-1 hAPPLond/Swe (APPL/S) AD mouse model. LM11A-31 reached brain concentrations known to inhibit degenerative signaling without toxicity or induction of hyperalgesia. It prevented deficits in novel object recognition after 2.5 months and, in a separate cohort, deficits in Y-maze performance after 3 months of treatment. Stereology studies found that the number and size of basal forebrain cholinergic neurons, which are normal in APPL/S mice, were unaffected. Neuritic dystrophy, however, was readily apparent in the basal forebrain, hippocampus and cortex, and was significantly reduced by LM11A-31, with no effect on amyloid levels. These studies reveal that p75NTR is an important and tractable in vivo drug target for AD, with LM11A-31 representing a novel class of therapeutic candidates.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 34, Issue 8, August 2013, Pages 2052-2063
نویسندگان
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