Display options
Cite
de Laat R, Meabon JS, Wiley JC, et al. LINGO-1 promotes lysosomal degradation of amyloid-β protein precursor. Pathobiol Aging Age Relat Dis. 2015;5:25796doi: 10.3402/pba.v5.25796.
de Laat, R., Meabon, J. S., Wiley, J. C., Hudson, M. P., Montine, T. J., & Bothwell, M. (2015). LINGO-1 promotes lysosomal degradation of amyloid-β protein precursor. Pathobiology of aging & age related diseases, 525796. https://doi.org/10.3402/pba.v5.25796
de Laat, Rian, et al. "LINGO-1 promotes lysosomal degradation of amyloid-β protein precursor." Pathobiology of aging & age related diseases vol. 5 (2015): 25796. doi: https://doi.org/10.3402/pba.v5.25796
de Laat R, Meabon JS, Wiley JC, Hudson MP, Montine TJ, Bothwell M. LINGO-1 promotes lysosomal degradation of amyloid-β protein precursor. Pathobiol Aging Age Relat Dis. 2015 Mar 09;5:25796. doi: 10.3402/pba.v5.25796. eCollection 2015. PMID: 25758563; PMCID: PMC4355507.
Copy Download .nbib Format: NLM
Share it on

Pathobiol Aging Age Relat Dis. 2015 Mar 09;5:25796. doi: 10.3402/pba.v5.25796. eCollection 2015.

LINGO-1 promotes lysosomal degradation of amyloid-β protein precursor.

Pathobiology of aging & age related diseases

Rian de Laat, James S Meabon, Jesse C Wiley, Mark P Hudson, Thomas J Montine, Mark Bothwell

Affiliations

  1. Immusoft, Seattle, WA, USA.
  2. Department of Psychiatry and Behavioral Sciences, University of Washington and Mental Illness Research Education and Clinical Center, VA Medical Center, Seattle, WA, USA.
  3. Department of Comparative Medicine, University of Washington, Seattle, WA, USA.
  4. Department of Physiology and Biophysics, University of Washington, Seattle, WA, USA.
  5. Department of Pathology, University of Washington, Seattle, WA, USA.
  6. Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA; [email protected].

PMID: 25758563 PMCID: PMC4355507 DOI: 10.3402/pba.v5.25796

Abstract

Sequential proteolytic cleavages of amyloid-β protein precursor (AβPP) by β-secretase and γ-secretase generate amyloid β (Aβ) peptides, which are thought to contribute to Alzheimer's disease (AD). Much of this processing occurs in endosomes following endocytosis of AβPP from the plasma membrane. However, this pathogenic mode of processing AβPP may occur in competition with lysosomal degradation of AβPP, a common fate of membrane proteins trafficking through the endosomal system. Following up on published reports that LINGO-1 binds and promotes the amyloidogenic processing of AβPP we have examined the consequences of LINGO-1/AβPP interactions. We report that LINGO-1 and its paralogs, LINGO-2 and LINGO-3, decrease processing of AβPP in the amyloidogenic pathway by promoting lysosomal degradation of AβPP. We also report that LINGO-1 levels are reduced in AD brain, representing a possible pathogenic mechanism stimulating the generation of Aβ peptides in AD.

Keywords: APP; Alzheimer's disease; AβPP proteolysis; LINGO; endosome; trafficking

References

  1. J Biol Chem. 2004 Jul 9;279(28):29639-46 - PubMed
  2. J Neurosci. 2007 Jul 18;27(29):7777-85 - PubMed
  3. J Neurosci. 2003 Jul 2;23(13):5425-36 - PubMed
  4. Mol Cell Proteomics. 2008 Jan;7(1):15-34 - PubMed
  5. J Cell Biol. 2007 Dec 3;179(5):951-63 - PubMed
  6. J Biol Chem. 2007 Nov 16;282(46):33313-25 - PubMed
  7. Neurogenetics. 2010 Oct;11(4):401-8 - PubMed
  8. Neuroreport. 2004 Oct 25;15(15):2397-400 - PubMed
  9. Neurosci Lett. 2011 Jan 7;487(2):174-6 - PubMed
  10. Nat Biotechnol. 2004 Dec;22(12):1533-7 - PubMed
  11. Parkinsonism Relat Disord. 2011 Sep;17(8):638-41 - PubMed
  12. Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):E2077-82 - PubMed
  13. Curr Mol Med. 2007 Nov;7(7):687-96 - PubMed
  14. Parkinsonism Relat Disord. 2010 Feb;16(2):109-11 - PubMed
  15. Mol Neurodegener. 2007 Jul 09;2:14 - PubMed
  16. Curr Opin Neurol. 2011 Aug;24(4):318-23 - PubMed
  17. Neuroepidemiology. 2011;37(1):1-10 - PubMed
  18. Nat Genet. 2009 Mar;41(3):277-9 - PubMed
  19. Cell Death Differ. 2009 Jan;16(1):70-8 - PubMed
  20. Neurosci Lett. 2012 Feb 10;509(1):9-12 - PubMed
  21. Mol Interv. 2006 Apr;6(2):74-6, 58 - PubMed
  22. Cells Tissues Organs. 2004;177(3):132-8 - PubMed
  23. Ann N Y Acad Sci. 1996 Jan 17;777:57-64 - PubMed
  24. Neuromolecular Med. 2003;4(1-2):21-36 - PubMed
  25. J Neurochem. 2005 Sep;94(5):1189-201 - PubMed
  26. Neuron. 2009 Sep 10;63(5):614-27 - PubMed
  27. Mol Brain. 2010 Apr 21;3:11 - PubMed
  28. J Biol Chem. 2007 Nov 9;282(45):32956-64 - PubMed
  29. Neurosci Lett. 2010 Mar 12;472(1):53-5 - PubMed
  30. J Cell Sci. 1996 May;109 ( Pt 5):991-8 - PubMed

Publication Types

Grant support