P2‐133: Okadaic acid‐induced tau phosphorylation in rat primary neurons: Involvement of the JNK pathway
Year: 2008
Type: article
Abstract: The defining neuropathological characteristics of Alzheimer's disease (AD) are the presence of aggregated amyloid in senile plaques and neurofibrillary tangles (NFT) consisting of hyperphosphorylated tau proteins. This abnormal hyperphosphorylation of tau makes it lose its normal function to stimulate microtubule assembly, gain toxic activity, and aggregate into NFTs. This may be the result of an increase in the activity of kinases involved in tau phosphorylation, or a decrease in the activity of phosphatases involved in the same pathways. One class of kinases showing increased expression and activity in Alzheimer's disease is the c-Jun N-terminal kinase (JNK), which consists of 3 isoforms. Pathological activation of JNK2 and JNK3 have been associated with plaques and tangles in AD and are thought to be at least partly responsible for neuronal cell death. In order to study this AD-like pathology in vitro, kinase pathways, including the JNK pathway, have been activated by the addition of a PP2A inhibitor, Okadaic Acid (OA) to primary neurons. Following the addition of OA the intracellular activation of JNK and the phosphorylation of tau have been analyzed using an automated cell-based imaging technique. We have determined the time course and concentration of OA that induces maximal JNK and tau phosphorylation prior to inducing cell death. We have measured the phosphorylation of JNK, c-Jun, and tau (at Ser 422, and Ser202/205 sites) and demonstrated that inhibition of the JNK pathway with a specific JNK inhibitor results in a decrease in tau phosphorylation. In this study we have characterized the role of the JNK pathway in mediating OA induced tau phosphorylation, providing a cellular model for studying this signaling pathway in a model of Alzheimer's Disease.
Source: Alzheimer s & Dementia
Authors: Jennifer Moore, Stan P. Nawoschik, Brian Ludwig, Beal McIlvain, Vasanti Anand, John Dunlop, Steven P. Braithwaite
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: PSP Association
OpenAlex ID: W1987911627