E3 ligase mahogunin (MGRN1) influences amyloid precursor protein maturation and secretion

3Citations
Citations of this article
11Readers
Mendeley users who have this article in their library.

Abstract

Altered processing of the Amyloid Precursor Protein (APP) is a well-recognized central pathogenic mechanism in Alzheimer's Disease (AD), and regulation of APP processing is a major focus of research in the AD field. However, how age-associated cellular and molecular changes contribute to changes in the amyloidogenic processing of APP have not been extensively clarified so far. We here provide evidence that the processing of APP is influenced by the e3 ubiquitin ligase Mahogunin (MGRN1), a neuroprotective molecule whose levels decrease with aging. Specifically, the expression of MGRN1 inhibits the maturation of APP by sequestering it in the secretory pathway. This sequestration significantly delayed the proteolytic processing of APP, resulting in a reduced β-amyloid (Aβ) peptide release into the extracellular environment. Accordingly, a reduction of MGRN1 levels in hippocampal neurons, as it occurs during physiological aging, leads to an increased Aβ40 and Aβ42 release. We therefore propose that age contributes to the amyloidogenic processing of APP by altering its intracellular trafficking along the secretory pathway due in part to the down-regulation of MGRN1.

Cite

CITATION STYLE

APA

Benvegnù, S., Wahle, T., & Dotti, C. G. (2017). E3 ligase mahogunin (MGRN1) influences amyloid precursor protein maturation and secretion. Oncotarget, 8(52), 89439–89450. https://doi.org/10.18632/oncotarget.20143

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free