SAGE KE Bulletin Board

Retromer: A trafficking complex involved in the regulation of Aß production in Alzheimer’s diseas

21 November 2005

Dietmar R. Thal

Highlights of the 35th Annual Meeting of the Society for Neuroscience 2005 in Washington DC:

Retromer: A trafficking complex involved in the regulation of Aß production in Alzheimer’s disease

The retromer is a trafficking complex composed of at least five different proteins. It is responsible for peptide trafficking from the endosome to the transgolgi network (1). Yu et al. (3) showed that the retromer is decreased in the entorhinal cortex of Alzheimer’s disease patients. In cell culture, they were able to show that downregulation of the retromer leads to a deficient trafficking of BACE from the endosome to the transgolgi network. Consequently, BACE increased in the endosome and at the cell membrane. In so doing, downregulation or dysfunction of the retromer resulted in an increaded production of Aß. In a second study, these authors presented a retromer knock-down mouse (4). In this mouse model the VPS35 protein - a component of the retromer - was knocked down. These mice were crossed with APP-transgenic mice.

In summary, the retromer complex appears to be an interesting target for the understanding of the regulation of BACE-activity and Aß production. The VPS35-protein, thereby, seems to play a critical role for the function of the retromer complex in Alzheimer’s disease as already shown by Small et al. (2).

References:

1. M.N.J.Seaman. Recycle your receptors with retromer. Trends Cell Biol. 2005; 68-75.

2. S.A.Small, K.Kent, A.Pierce, C.Leung, M.S.Kang, H.Okada, L.Honig, J.- P.Vonsattel, T.-W.Kim. Model-guided microarray implicates the retromer complex in Alzheimer’s disease. Ann Neurol. In press.

3. R.Yu, I.Flore, K.Kent, T.Kim, L.Honig, S.A.Small. The retromer and Alzheimer's disease: cellular mechanisms of increased A�2 production in sporadic disease Program No. 661.9. 2005 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience

4. R.Yu, I.Flores, A.Staniszewski, T.Kim, P.S.G.Hyslop, D.Westaway, O.Arancio, L.Honig, S.A.Small. The retromer and Alzheimer's disease: characterizing retromer knock - down mice with and without APP mutations Program No. 661.8. 2005 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience



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