Modifying Rap1-signalling by targeting Pde6δ is neuroprotective in models of Alzheimer's disease.

ABSTRACT:

Background

Neuronal Ca²⁺ dyshomeostasis and hyperactivity play a central role in Alzheimer's disease pathology and progression. Amyloid-beta together with non-genetic risk-factors of Alzheimer's disease contributes to increased Ca²⁺ influx and aberrant neuronal activity, which accelerates neurodegeneration in a feed-forward fashion. As such, identifying new targets and drugs to modulate excessive Ca²⁺ signalling and neuronal hyperactivity, without overly suppressing them, has promising therapeutic potential.

Methods

Here we show, using biochemical, electrophysiological, imaging, and behavioural tools, that pharmacological modulation of Rap1 signalling by inhibiting its interaction with Pde6δ normalises disease associated Ca²⁺ aberr

SUBMITTER: Dumbacher M 

PROVIDER: S-EPMC6158915 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature