Structure-function relationships of the VILlP-1 - a4ß2 nAChR interaction - implications for nicotine-induced functional up-regulation of the a4ß2 nicotinic acetylcholine receptor

• Applicants: Professor Dr. Karl-Heinz Braunewell; Professorin Dr. Denise Manahan-Vaughan
• Subject Area: Biological Psychiatry
• Term: from 2006 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 24839276

• Final Report Year: 2015

Final Report Abstract

In in vitro and in vivo studies, we demonstrated that Aβ-treatment has potent detrimental effects on the profile and longevity of hippocampal LTP. The VILIP-1-derived L27 peptide enhances LTP and can rescue from detrimental Aβ effects on LTP. Both effects are phospholipid and nAChR-dependent (MLA and Annexin). Since VILIP-1-KO +/- show reduced LTP, and the detrimental Aβ effect is enhanced in VILIP-1-KO with lowered VILIP- 1 levels confirms a role of VILIP-1 in synaptic plasticity and memory. Thus, if Aβ, nicotinic receptors, VILIP-1 and synaptic plasticity are linked, then the VILIP-1-mimetic L27 peptide may serve as a therapeutic peptide.

Publications

• (2011) Association of VSNL1 with schizophrenia, frontal cortical function, and biological significance for its gene product as a modulator of cAMP levels and neuronal morphology. Transl. Psychiatry 1
  Braunewell KH, Dwary A D, Richter F, Trappe K, Zhao C, Giegling I, Schönrath K and D. Rujescu
  (See online at https://doi.org/10.1038/tp.2011.20)
• (2012). The visinin-like proteins VILIP-1 and VILIP-3 in Alzheimer's disease-old wine in new bottles. Front. Mol. Neurosci. 5:20
  Braunewell KH
  (See online at https://doi.org/10.3389/fnmol.2012.00020)
• (2014) Regulation of hippocampal synaptic plasticity thresholds and changes in exploratory and learning behavior in dominant negative NPR-B mutant rats, Frontiers Mol Neurosci. 7:95
  Barmashenko G, Buttgereit J, Zcelik C, Herring N, Bader M, Manahan-Vaughan D, Braunewell KH
  (See online at https://doi.org/10.3389/fnmol.2014.00095)