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Pathological mechanism
Name
Okadaic acid mediates tau phosphorylation via L channel activation
Description
Hypothesis
Dendritic Hypothesis - Ca++ currents
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Extracelular pathological element
Intracelular pathological element
MAP Kinase
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Pathological action
Induces
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Process
Tau hyperphosphorylation
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Process action
Activates
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Transmitter(s)
Receptor(s)
Channel(s)
I L high threshold
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Pharmacological Agent
Okadaic Acid
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Pharmacological Action
Increases
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Brain region
Neuron
Cell model
SH-SY-5Y human neuroblastoma cells
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Cellular compartment
PubMed ID
14559148
Citation
14559148
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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
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Stage
Question
Claim
Aß causes increased Ca++ influx by activation of L-type Ca++ channels
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Other categories referring to "
Okadaic acid mediates tau phosphorylation via L channel activation
"
Revisions:
11
Last time:
11/21/2008 10:18:59 AM
Reviewer:
Pradeep Mutalik
Owner:
Tom Morse
This database was supported by the Human Brain Project (NIDCD, NIMH, NIA, NICD, NINDS) and MURI (Multidisciplinary University Research Initiative). It is now supported by RO1 DC 009977 from the National Institute for Deafness and other Communication Disorders.
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