Volume 8 Supplement 1

Molecular Neurodegeneration: Basic biology and disease pathways

Open Access

The role of SorLA in neurotrophic activity and complex behavior

  • Simon Glerup1,
  • Mart Saarma2 and
  • Anders Nykjaer1
Molecular Neurodegeneration20138(Suppl 1):P19

https://doi.org/10.1186/1750-1326-8-S1-P19

Published: 13 September 2013

SorLA binds amyloid precursor protein (APP) in the trans-Golgi network and protects it against proteolysis by both the alpha- and beta-secretases, preventing the generation of toxic amyloid-beta peptide. We have recently found that SorLA also affects neuronal function in a different manner by acting as sorting receptor for the neurotrophic factor GDNF and its receptors GFRα1 and RET, directing them from the cell surface to endosomes. Through this mechanism, GDNF is targeted to lysosomes and degraded while GFRα1 and RET recycles, creating an efficient GDNF clearance pathway. SorLA thereby influences a number of neuronal systems known to depend on GDNF activity including the dopaminergic system and the hippocampus. Accordingly, mice with altered SorLA expression exhibit altered reward and memory function, and a behavioral phenotype characterized by altered anxiety, hyperactivity, and response to psychostimulants.

Authors’ Affiliations

(1)
Biomedicine, Aarhus University
(2)
Institute of Biotechnology, University of Helsinki

Copyright

© Glerup et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Advertisement