With the Help of a Chaperone

  • Author: Melania Tesio
  • Published: 12 May 2014
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA
  • Source / Publisher: Nature Chemical Biology/Nature Publishing Group
thumbnail image: With the Help of a Chaperone

Alzheimer's, a severe neurological disease, is characterized by the progressive loss of neurons. This phenomenon originates from the cleavage of the amyloid-precursor protein (APP) into toxic fragments that accumulate in neurons, thereby causing their death.


Scott Small, Columbia University, New York, USA, and co-workers discovered a way to prevent this process. When APP localizes in specific cellular organelles (endosomes) it is cleaved into toxic fragments. Thus, the researchers developed a strategy to drive APP out of this cellular compartment. The scientists developed R55 (pictured), a small molecule that acts as a chaperon and enhances the stability and activity of retromer, a multiprotein complex that transports APP away from endosomes. As a consequence, R55 reduced the cleavage of APP and, therefore, the death of neurons.
R55 may represent a novel therapeutic option for treating Alzheimer disease.


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