Cellular Pathway Implicated in Alzheimer's Disease
Pathway involved in increased production of amyloid-beta
FRIDAY, March 21 (HealthDay News) -- A cellular signaling pathway is involved in increased production of amyloid-beta (Aβ) in mice and could be targeted in Alzheimer's disease, researchers report in the March 13 issue of Neuron.
Yi Wen, from the Taub Institute at Columbia University Medical Center in New York City, and colleagues overproduced p25, an activator of cyclin-dependent kinase 5 (cdk5), which they note has been implicated in the pathogenesis of Alzheimer's disease, in cells and in mice.
The researchers found that the beta site Aβ precursor protein (APP) cleaving enzyme 1 (BACE1) and signal transducer and activator of transcription 3 proteins were elevated in mice overproducing p25. The increased BACE1 levels were associated with increased amyloidogenic processing of APP, which could be reversed with a cdk5 inhibitor.
"Overall, given that p25/cdk5 significantly enhances Aβ production in vivo, inhibition of p25/cdk5 may be an appealing therapeutic approach for the treatment or prevention of Alzheimer's disease," Wen and colleagues conclude.