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

Pathobiology of Aging & Age Related Diseases
Rian de LaatMark Bothwell

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.

References

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Citations

Nov 8, 2015·Molecular and Cellular Neurosciences·James S MeabonMark Bothwell
Jul 6, 2015·Neuroscience and Biobehavioral Reviews·Jessica L Andrews, Francesca Fernandez-Enright
Feb 4, 2016·Trends in Pharmacological Sciences·Carole DeytsAngèle T Parent

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Methods Mentioned

BETA
transfection
dissection
confocal microscopy

Software Mentioned

Elements
NIH ImageJ
NIS

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