Role of SORLA in Transport of TrkB and APP in Alzheimer's Disease
To sort out this complicated interaction of proteins, Dr. Rohe and collaborators will find out exactly how SORLA works in concert with APP and TrkB. Their discoveries could potentially lead to a new disease-modifying treatment designed to increase the levels of SORLA in the brain in order to prevent the release of beta-amyloid and stop plaque formation.
So far, Dr. Rohe’s team was able to document that SORLA not only regulates the breakdown of APP but also the transport of the BDNF receptor, called TrkB. Binding of BDNF to TrkB is central for supporting the function and survival of neurons. Because of the impaired transport of TrkB, BDNF signals received by neurons lacking SORLA are reduced. This reduction renders affected neurons vulnerable and disrupts their proper function. In support of this hypothesis, Dr. Rohe identified that SORLA deficiency disrupts the function of several brain proteins that are important for proper communication between nerve cells. Intriguingly, the disruption of these proteins coincided with impaired learning and memory in SORLA-deficient mice, further underscoring the relevance of this signaling pathway for cognitive functions. Since low levels of SORLA have been documented in AD patients, Dr. Rohe’s data provide an explanation of how low levels of the receptor protein may translate into memory deficits.
About the Researcher
Rohe M, Hartl D, Fjorback AN, Willnow TE (2013) SORLA-mediated trafficking of TrkB enhances the response of neurons to BDNF. PLoS One, accepted for publication.
Hartl D#, Klatt S, Roch M, Konthur Z, Klose J, Willnow TE, and Rohe M (2013) Soluble alpha-APP (sAPPalpha) regulates CDK5 expression and activity in neurons. PLoS One, 8(6):e65920.
First published on: July 6, 2011
Last modified on: March 22, 2013