References
Query Results -- Details
MGI Accession ID: MGI:3801250
J Number: J:137577
Other Accession IDs:
Title: Sortilin-related receptor with A-type repeats (SORLA) affects the amyloid precursor protein-dependent stimulation of ERK signaling and adult neurogenesis.
Authors: Rohe M; Carlo AS; Breyhan H; Sporbert A; Militz D; Schmidt V; Wozny C; Harmeier A; Erdmann B; Bales KR; Wolf S; Kempermann G; Paul SM; Schmitz D; Bayer TA; Willnow TE; Andersen OM
Journal: J Biol Chem
Volume: 283
Issue: 21
Date: 2008 May 23
Year: 2008
Pages: 14826-34
Review Status: Peer Reviewed
Abstract:
Sortilin-related receptor with A-type repeats (SORLA) is a sorting receptor that impairs processing of amyloid precursor protein (APP) to soluble (s) APP and to the amyloid beta-peptide in cultured neurons and is poorly expressed in patients with Alzheimer disease (AD). Here, we evaluated the consequences of Sorla gene defects on brain anatomy and function using mouse models of receptor deficiency. In line with a protective role for SORLA in APP metabolism, lack of the receptor results in increased amyloidogenic processing of endogenous APP and in aggravated plaque deposition when introduced into PDAPP mice expressing mutant human APP. Surprisingly, increased levels of sAPP caused by receptor deficiency correlate with pro-found stimulation of neuronal ERK signaling and with enhanced neurogenesis, providing in vivo support for neurotrophic functions of sAPP. Our data document a role for SORLA not only in control of plaque burden but also in APP-dependent neuronal signaling and suggest a molecular explanation for increased neurogenesis observed in some AD patients.
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