| First Author | Patnaik A | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 13322 |
| PubMed ID | 32770070 | Mgi Jnum | J:299809 |
| Mgi Id | MGI:6490694 | Doi | 10.1038/s41598-020-70153-4 |
| Citation | Patnaik A, et al. (2020) Signaling via the p75 neurotrophin receptor facilitates amyloid-beta-induced dendritic spine pathology. Sci Rep 10(1):13322 |
| abstractText | Synapse and dendritic spine loss induced by amyloid-beta oligomers is one of the main hallmarks of the early phases of Alzheimer's disease (AD) and is directly correlated with the cognitive decline typical of this pathology. The p75 neurotrophin receptor (p75(NTR)) binds amyloid-beta oligomers in the nM range. While it was shown that microM concentrations of amyloid-beta mediate cell death, the role and intracellular signaling of p75(NTR) for dendritic spine pathology induced by sublethal concentrations of amyloid-beta has not been analyzed. We describe here p75(NTR) as a crucial binding partner in mediating effects of soluble amyloid-beta oligomers on dendritic spine density and structure in non-apoptotic hippocampal neurons. Removing or over-expressing p75(NTR) in neurons rescues or exacerbates the typical loss of dendritic spines and their structural alterations observed upon treatment with nM concentrations of amyloid-beta oligomers. Moreover, we show that binding of amyloid-beta oligomers to p75(NTR) activates the RhoA/ROCK signaling cascade resulting in the fast stabilization of the actin spinoskeleton. Our results describe a role for p75(NTR) and downstream signaling events triggered by binding of amyloid-beta oligomers and causing dendritic spine pathology. These observations further our understanding of the molecular mechanisms underlying one of the main early neuropathological hallmarks of AD. |
