When the co-receptor sortilin is present at the cell surface, proNGF preferentially interacts with a p75NTR:sortilin complex. Thus, proNGF, which does not bind TRKA, discriminates between TRKA and p75NTR, in cells that express both receptors. The same is true for proBDNF. Pro-neurotrophin binding to p75NTR:sortilin activates an apoptotic cascade, which may be involved in cell death after injury, and in neurodegenerative diseases such as Alzheimer's dementia.
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