Retromer is a protein assembly that has a central role in endosomal trafficking, and retromer dysfunction has been linked to a growing number of neurological disorders. First linked to Alzheimer disease, retromer dysfunction causes a range of pathophysiological consequences that have been shown to contribute to the core pathological features of the disease. Genetic studies have established that retromer dysfunction is also pathogenically linked to Parkinson disease, although the biological mechanisms that mediate this link are only now being elucidated. Most recently, studies have shown that retromer is a tractable target in drug discovery for these and other disorders of the nervous system.
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The authors thank the US National Institute on Ageing, US National Institutes of Health grants AG025161 and AG08702, The Alzheimer's Association, The McKnight Endowment for Neuroscience, the Ellison Medical Foundation and The Fidelity Biosciences Research Initiative for funding, and give special thanks to S. Weninger for advice and encouragement. The authors also thank G. Di Paolo for discussions regarding the manuscript.
The authors declare no competing financial interests.
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Small, S., Petsko, G. Retromer in Alzheimer disease, Parkinson disease and other neurological disorders. Nat Rev Neurosci 16, 126–132 (2015). https://doi.org/10.1038/nrn3896
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