Pathological mechanism

Data

Name Abeta inhibits PAK, stimulates ROCK and impairs synapses by TLR signaling

Description

Hypothesis Synapse Loss Show Other

Extracelular pathological element beta Amyloid Show Other

Intracelular pathological element Rho kinases (ROCK1/2) Show Other

Pathological action Disrupts Show Other

Process Synaptic plasticity Show Other

Process action

Transmitter(s)

Receptor(s)

Channel(s)

Pharmacological Agent

Pharmacological Action

Brain region

Neuron

Cell model

Cellular compartment

PubMed ID 18466762

Citation

AlzWeb

Notes Synaptic dysfunction is a sensitive parameter of the AD pathology. Rho GTPases and the Rho kinases, ROCK1/2, and PAK1-3, are important regulators of synaptic plasticity, especially in maintaining the actin cytoskeleton of dendritic spines. Beta-amyloid oligomers can inhibit PAK and stimulate ROCK-mediated signaling. Both of these effects enhance the disassembly of synaptic actin filaments and ultimately evoke synaptic loss. Brain tissue in AD recognizes the beta-amyloid peptide oligomers as foreign protein particles and mounts an inflammatory defense via Toll-like receptor (TLR) signaling which causes synaptic impairment. Salminen, A., Suuronen, T., & Kaarniranta, K. (2008). ROCK, PAK, and toll of synapses in alzheimer's disease. Biochemical and Biophysical Research Communications, 371(4), 587-590.

Pathology Alzheimer Show Other

Stage Early Show Other

Question Exclude - Biochemistry

Claim