Kinesin-mediated axonal transport of a membrane compartment containing β-secretase and presenilin-1 requires APP

@article{Kamal2001KinesinmediatedAT,
  title={Kinesin-mediated axonal transport of a membrane compartment containing $\beta$-secretase and presenilin-1 requires APP},
  author={Adeela Kamal and Angels Almenar-Queralt and James F. LeBlanc and Elizabeth A. Roberts and Lawrence S B Goldstein},
  journal={Nature},
  year={2001},
  volume={414},
  pages={643-648}
}
Proteolytic processing of amyloid precursor protein (APP) generates amyloid-β peptide and has been implicated in the pathogenesis of Alzheimer's disease. However, the normal function of APP, whether this function is related to the proteolytic processing of APP, and where this processing takes place in neurons in vivo remain unknown. We have previously shown that the axonal transport of APP in neurons is mediated by the direct binding of APP to the kinesin light chain subunit of kinesin-I, a… 
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  • B. Tang
  • Biology
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  • 2009
TLDR
Changes in post-Golgi membrane trafficking in aging neurons that may influence APP processing is particularly relevant to late-onset, idiopathic AD.
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TLDR
It is shown that reduction of presenilin (PS) or suppression of gamma-secretase activity substantially increases anterograde and retrograde velocities for APP vesicles, suggesting that axonal transport defects induced by loss of PS-mediated regulatory effects on APP-vesicle motility could be a major cause of neuronal and synaptic defects observed in Alzheimer's Disease (AD) pathogenesis.
Inhibition of APP Trafficking by Tau Protein Does Not Increase the Generation of Amyloid‐β Peptides
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The results indicate that APP is transported on vesicles distinct from the secretase components and that amyloid‐β is not generated in transit when transport is blocked by tau.
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