Finding an Alzheimer-FAT link

© 2004 Nature Publishing GroupConstantly on the run, membrane-bounded organelles (MBOs) in neurons deliver proteins from cell bodies to axons. A recent study by Scott Brady and colleagues at the University of Illinois suggests that disruption of this anterograde fast axonal transport (FAT) may contribute to Alzheimer disease pathogenesis via a novel pathway locally regulating glycogen synthase kinase-3 (GSK3) activity.1According to this study, cyclin-dependent kinase 5-inhibition allows pro

Bosede Adenekan
Jul 18, 2004
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© 2004 Nature Publishing Group

Constantly on the run, membrane-bounded organelles (MBOs) in neurons deliver proteins from cell bodies to axons. A recent study by Scott Brady and colleagues at the University of Illinois suggests that disruption of this anterograde fast axonal transport (FAT) may contribute to Alzheimer disease pathogenesis via a novel pathway locally regulating glycogen synthase kinase-3 (GSK3) activity.1

According to this study, cyclin-dependent kinase 5-inhibition allows protein phosphatase 1 to activate GSK3, which phosphorylates the motor protein kinesin, causing it to detach from MBOs. Without kinesin, no protein delivery occurs. Constitutively active GSK3 in squid axoplasm causes neurite retraction, apoptosis, and embryonic lethality; therefore, local GSK3 regulation in neurons must be necessary for survival. "You want to be able to turn on GSK3 in the right location; [otherwise] transport doesn't work and the nerve suffers," says Brady. They observed such defective FAT and increased GSK3 activity...

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