Abstract
Mutations in presenilin 1 (PS1) cause early-onset familial Alzheimers disease (FAD). Although FAD accounts for less than 5% of all cases of Alzheimers disease (AD), extensive analyses of PS1 function have elucidated an important neuronal mechanism underling AD pathogenesis. PS1 is considered to be an essential component of γ-secretase, which cleaves amyloid precursor protein (APP) at the transmembrane region and releases amyloid β (Aβ) peptide. In addition to this well-documented function, a growing amount of evidence suggests that PS1 is involved in the intracellular trafficking of selected membrane proteins (i.e. APP, nicastrin, trkB, telencephalin). Recently, we have also shown that PS1 is involved in the trafficking of N-cadherin from the endoplasmic reticulum to the plasma membrane via the microtubule network. N-cadherin is localized at the synaptic junctional complex, providing an adhesive force across the synaptic cleft, and the its regulation is crucial for the neuron to exert its specific function, i.e. synaptic activity. In a mature neuron, polarized targeting of proteins from the cell body to the axonal and dendritic processes is essential for its proper function, especially, for the maintenance of synaptic function. Alterations in protein transport caused by a dysfunction in PS1 could lead to a disturbance in synaptic transmission and finally to neurodegeneration. This article will review the current knowledge of PS1 function in protein trafficking and discuss its potential role in AD pathogenesis.
Keywords: Alzheimer disease, Presenilin, Amyloid Precursor Protein, Amyloid b peptide, Protein Trafficking
Current Alzheimer Research
Title: Protein Trafficking and Alzheimers Disease
Volume: 1 Issue: 1
Author(s): Kengo Uemura, Akira Kuzuya and Shun Shimohama
Affiliation:
Keywords: Alzheimer disease, Presenilin, Amyloid Precursor Protein, Amyloid b peptide, Protein Trafficking
Abstract: Mutations in presenilin 1 (PS1) cause early-onset familial Alzheimers disease (FAD). Although FAD accounts for less than 5% of all cases of Alzheimers disease (AD), extensive analyses of PS1 function have elucidated an important neuronal mechanism underling AD pathogenesis. PS1 is considered to be an essential component of γ-secretase, which cleaves amyloid precursor protein (APP) at the transmembrane region and releases amyloid β (Aβ) peptide. In addition to this well-documented function, a growing amount of evidence suggests that PS1 is involved in the intracellular trafficking of selected membrane proteins (i.e. APP, nicastrin, trkB, telencephalin). Recently, we have also shown that PS1 is involved in the trafficking of N-cadherin from the endoplasmic reticulum to the plasma membrane via the microtubule network. N-cadherin is localized at the synaptic junctional complex, providing an adhesive force across the synaptic cleft, and the its regulation is crucial for the neuron to exert its specific function, i.e. synaptic activity. In a mature neuron, polarized targeting of proteins from the cell body to the axonal and dendritic processes is essential for its proper function, especially, for the maintenance of synaptic function. Alterations in protein transport caused by a dysfunction in PS1 could lead to a disturbance in synaptic transmission and finally to neurodegeneration. This article will review the current knowledge of PS1 function in protein trafficking and discuss its potential role in AD pathogenesis.
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Cite this article as:
Uemura Kengo, Kuzuya Akira and Shimohama Shun, Protein Trafficking and Alzheimers Disease, Current Alzheimer Research 2004; 1 (1) . https://dx.doi.org/10.2174/1567205043480528
DOI https://dx.doi.org/10.2174/1567205043480528 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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