The Intersection of NGF/TrkA Signaling and Amyloid Precursor Protein Processing in Alzheimer’s Disease Neuropathology
AbstractDysfunction of nerve growth factor (NGF) and its high-affinity Tropomyosin receptor kinase A (TrkA) receptor has been suggested to contribute to the selective degeneration of basal forebrain cholinergic neurons (BFCN) associated with the progressive cognitive decline in Alzheimer's disease (AD). The aim of this review is to describe our progress in elucidating the molecular mechanisms underlying the dynamic interplay between NGF/TrkA signaling and amyloid precursor protein (APP) metabolism within the context of AD neuropathology. This is mainly based on the finding that TrkA receptor binding to APP depends on a minimal stretch of ~20 amino acids located in the juxtamembrane/extracellular domain of APP that carries the α- and β-secretase cleavage sites. Here, we provide evidence that: (i) NGF could be one of the “routing” proteins responsible for modulating the metabolism of APP from amyloidogenic towards non-amyloidogenic processing via binding to the TrkA receptor; (ii) the loss of NGF/TrkA signaling could be linked to sporadic AD contributing to the classical hallmarks of the neuropathology, such as synaptic loss, β-amyloid peptide (Aβ) deposition and tau abnormalities. These findings will hopefully help to design therapeutic strategies for AD treatment aimed at preserving cholinergic function and anti-amyloidogenic activity of the physiological NGF/TrkA pathway in the septo-hippocampal system. View Full-Text
Scifeed alert for new publicationsNever miss any articles matching your research from any publisher
- Get alerts for new papers matching your research
- Find out the new papers from selected authors
- Updated daily for 49'000+ journals and 6000+ publishers
- Define your Scifeed now
Canu, N.; Amadoro, G.; Triaca, V.; Latina, V.; Sposato, V.; Corsetti, V.; Severini, C.; Ciotti, M.T.; Calissano, P. The Intersection of NGF/TrkA Signaling and Amyloid Precursor Protein Processing in Alzheimer’s Disease Neuropathology. Int. J. Mol. Sci. 2017, 18, 1319.
Canu N, Amadoro G, Triaca V, Latina V, Sposato V, Corsetti V, Severini C, Ciotti MT, Calissano P. The Intersection of NGF/TrkA Signaling and Amyloid Precursor Protein Processing in Alzheimer’s Disease Neuropathology. International Journal of Molecular Sciences. 2017; 18(6):1319.Chicago/Turabian Style
Canu, Nadia; Amadoro, Giuseppina; Triaca, Viviana; Latina, Valentina; Sposato, Valentina; Corsetti, Veronica; Severini, Cinzia; Ciotti, Maria Teresa; Calissano, Pietro. 2017. "The Intersection of NGF/TrkA Signaling and Amyloid Precursor Protein Processing in Alzheimer’s Disease Neuropathology." Int. J. Mol. Sci. 18, no. 6: 1319.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.