Molecular characterization of Netrin-1 and APP receptor binding: New leads to block the progression of senile plaques in Alzheimer's disease

Biochemical and Biophysical Research Communications
Franck BorelJean-Luc Ferrer

Abstract

Alzheimer's disease is a growing concern in the context of the increasing lifespan of the populations. The work presented here is part of the fight against this threat. It supports a therapeutic approach to reduce the incidence of Alzheimer's disease, taking advantage of the specific binding of several domains of Netrin-1 to the β-amyloid precursor protein. This basic knowledge shall then be used to predict, design or characterize lead compounds that may in turn inhibit/delay Alzheimer's disease's progression, extending the therapeutic offer of the other leads already being investigated in this line. The present work is focused on the interaction of the various portions of APP with the three domains of Netrin-1, the so-called LamNT, EGF-like and NTR domains respectively. It reveals in detail which portions of APP and Netrin-1 are specifically involved in these interactions, using ELISA technique in combination with protein-protein binding simulations. So far unsuspected interaction sites located in Netrin-1 EGF-like and NTR domains open possibilities for new therapeutic approaches in which these sites will be specifically targeted.

Citations

Jul 25, 2017·Reproduction : the Official Journal of the Society for the Study of Fertility·Joanna BudnaBartosz Kempisty
Aug 2, 2018·Clinical and Experimental Pharmacology & Physiology·Elham ZamaniParvaneh Mohseni-Moghaddam
Jul 17, 2019·Experimental Neurobiology·Won Suk LeeKyoungho Suk
Dec 14, 2017·International Journal of Molecular Sciences·Joanna BudnaBartosz Kempisty
May 24, 2020·International Journal of Molecular Sciences·Sung Wook Kim, Kyong-Tai Kim

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