Editors' ChoiceNeuroscience

GPR3 and Alzheimer’s Disease

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Sci. Signal.  17 Feb 2009:
Vol. 2, Issue 58, pp. ec66
DOI: 10.1126/scisignal.258ec66

Accumulation of the amyloid-β peptide (Aβ) is thought to represent a central problem in the pathogenesis of Alzheimer’s disease. Aside from the two proteases responsible for the generation of this peptide, few additional potential drug targets for the treatment of Alzheimer’s disease have emerged. Thathiah et al. describe an extensive high-throughput screen that sought to identify modulators of Aβ production. This functional genomics effort identified the G protein–coupled receptor GPR3 as a modulator of Aβ production. GPR3 has been mapped to a chromosomal locus associated with increased risk for Alzheimer’s disease; is highly expressed in hippocampus and cortex, regions of the brain that strongly correlate with Alzheimer's disease progression; and thus represents an attractive drug target.

A. Thathiah, K. Spittaels, M. Hoffmann, M. Staes, A. Cohen, K. Horré, M. Vanbrabant, F. Coun, V. Baekelandt, A. Delacourte, D. F. Fischer, D. Pollet, B. De Strooper, P. Merchiers, The orphan G protein–coupled receptor 3 modulates amyloid-beta peptide generation in neurons. Science 323, 946–951 (2009). [Abstract] [Full Text]