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α-Secretase cleavage of p75

Cleavage of p75 neurotrophin receptor is linked to Alzheimer’s disease

Molecular Psychiatry volume 21, pages 300–301 (2016)Cite this article

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An underappreciated aspect of neurotrophin receptors is the proteolytic cleavage of the p75 neurotrophin receptor, which gives rise to a soluble extracellular domain (ECD). This event occurs frequently, resulting in large amounts of shedding of the p75 ECD, which was easily detected in urine, plasma and amniotic fluid.1 Moreover, the shedding of the ECD is developmentally regulated and increases after nerve lesion. The biological consequences of the production of the ECD half of p75 have remained a mystery for decades.

The appearance of the p75 ECD was originally detected in Schwann cells after axotomy,1 but has been also found in the brain after injury or pathological conditions.2 The recent study by Yao et al.2 indicates that one function of the p75 ECD is to protect against amyloid-beta peptide toxicity. This is a very intriguing observation, given that p75 receptor signaling has been associated with neurodegeneration and cell death through the binding to pro-neurotrophins.3 Why do neurotrophins induce a cell death signal, as well as produce trophic support to many neuronal populations?

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  1. Departments of Cell Biology, Physiology and Neuroscience and Psychiatry, Skirball Institute of Biomolecular Medicine, New York University Langone School of Medicine, New York, NY, USA

    M V Chao

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  1. M V Chao
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Correspondence to M V Chao.

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Chao, M. Cleavage of p75 neurotrophin receptor is linked to Alzheimer’s disease. Mol Psychiatry 21, 300–301 (2016). https://doi.org/10.1038/mp.2015.214

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