PTK2B/Pyk2 overexpression improves a mouse model of Alzheimer's disease.

PTK2B/Pyk2 overexpression improves a mouse model of Alzheimer's disease.
Exp Neurol. 2018 May 24;:
Authors: Giralt A, de Pins B, Cifuentes-Díaz C, López-Molina L, Farah AT, Tible M, Deramecourt V, Arold S, Ginés S, Hugon J, Girault JA
Abstract
Pyk2 is a Ca2+-activated non-receptor tyrosine kinase enriched in forebrain neurons and involved in synaptic regulation. Human genetic studies associated PTK2B, the gene coding Pyk2, with risk for Alzheimer's disease (AD). We previously showed that Pyk2 is important for hippocampal function, plasticity, and spine structure. However, its potential role in AD is unknown. To address this question we used human brain samples and 5XFAD mice, an amyloid mouse model of AD expressing mutated human amyloid precursor protein and presenilin1. In the hippocampus of 5XFAD mice and in human AD patients' cortex and hippocampus, Pyk2 total levels were normal. However, Pyk2 Tyr-402 phosphorylation levels, reflecting its autophosphorylation-dependent activity, were reduced in 5XFAD mice at 8 months of age but at 3 months. We crossed these mice with Pyk2-/- mice to generate 5XFAD animals devoid of Pyk2. At 8 months the phenotype of 5XFAD x Pyk2-/- double mutant mice was not different from that of 5XFAD. In contrast, overexpression of Pyk2 in the hippocampus of 5XFAD mice, using adeno-associated virus, rescued autophosphorylated Pyk2 levels and improved synaptic markers and performance in several behavior...

Source: Experimental Neurology - May 24, 2018 Category: Neurology Authors: Giralt A, de Pins B, Cifuentes-Díaz C, López-Molina L, Farah AT, Tible M, Deramecourt V, Arold S, Ginés S, Hugon J, Girault JA Tags: Exp Neurol Source Type: research