Pathological mechanism

Data

Name Okadaic acid mediates tau phosphorylation via L channel activation

Description

Hypothesis Dendritic Hypothesis - Ca++ currents Show Other

Extracelular pathological element

Intracelular pathological element MAP Kinase Show Other

Pathological action Induces Show Other

Process Tau hyperphosphorylation Show Other

Process action Activates Show Other

Transmitter(s)

Receptor(s)

Channel(s) I L high threshold Show Other

Pharmacological Agent Okadaic Acid Show Other

Pharmacological Action Increases Show Other

Brain region

Neuron

Cell model SH-SY-5Y human neuroblastoma cells Show Other

Cellular compartment

PubMed ID 14559148

Citation Okadaic acid mediates tau phosphorylation via sustained activation of the L-voltage-sensitive calcium channel. Show Other

AlzWeb

Notes Prior studies indicate that one of the kinases that phosphorylates tau (mitogen-activated protein kinase, or MAP kinase) does so at least in part indirectly within intact neuronal cells by phosphorylating and activating the L-voltage-sensitive calcium channel. Resultant calcium influx then fosters tau phosphorylation via one or more calcium-activated kinases. okadaic acid (OA) similarly may increase tau phosphorylation via sustained activation of the L-voltage-sensitive calcium channel. OA increased phospho-tau as indicated by increased immunoreactivity towards an antibody (PHF-1) directed against paired helical filaments from AD brain. This increase was blocked by co-treatment with the channel antagonist nimodipine. ... Okadaic acid (OA) treatment increased channel phosphorylation. The increases in calcium influx, PHF-1 immunoreactivity and channel phosphorylation were all attenuated by co-treatment with PD98059, which inhibits MAP kinase activity, suggesting that OA mediates these effects at least in part via sustained activation of MAP kinase. (Ekinci FJ et al. 2003)

Pathology Alzheimer Show Other

Stage

Question

Claim Aß causes increased Ca++ influx by activation of L-type Ca++ channels Show Other