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Transthyretin neuroprotection in Alzheimer's disease is dependent on proteolysis

Neurobiology of Aging. 2017; 
Catarina S.SilvaabJessicaEiraabcCarlos A.RibeirodÂngelaOliveirabdMónica M.SousabeIsabelCardosobdMárcia A.Liz
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Peptide Synthesis TTR proteolytic activity was tested with the fluorogenic peptide Abz-VHHQKL-EDDnp (Genscript). TTR (5 μM total protein) was added to the substrate (5 μM) in a final volume of 100 μL of reaction buffer (50 mM Tris/HCl, pH 7.5). Hydrolysis of the peptide at 37 °C was followed by measuring the fluorescence at λem = 420 nm and λex = 320 nm in an Fmax plate reader (Molecular Devices) for 60 minutes. Get A Quote

摘要

The deposition of amyloid β peptide (Aβ) in the hippocampus is one of the major hallmarks of Alzheimer's disease, a neurodegenerative disorder characterized by memory loss and cognitive impairment. The modulation of Aβ levels in the brain results from an equilibrium between its production from the amyloid precursor protein and removal by amyloid clearance proteins, which might occur via enzymatic (Aβ-degrading enzymes) or nonenzymatic (binding/transport proteins) reactions. Transthyretin (TTR) is one of the major Aβ-binding proteins acting as a neuroprotector in AD. In addition, TTR cleaves Aβ peptide in vitro. In this work, we show that proteolytically active TTR, and not the inactive form... More

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