NGF and APP Interplay: Focus on YENPTY Motif of Amyloid Precursor Protein and Y682 Residue

NGF and APP Interplay: Focus on YENPTY Motif of Amyloid Precursor Protein and Y682 Residue

Cholinergic deficits originated from NGF metabolism disruption, represent one of the early changes in Alzheimer’s disease, where abnormal deposition of β-amyloid peptide (Aβ) and phosphorylated Tau define the neuropathological hallmarks of the disorder. A failure in NGF maturation can promote pro-apoptotic pathway activation, through p75 receptor; while lack of NGF signalling can generate an atypical TrkA receptor phosphorylation resulting in neuronal cell death and Aβ toxicity. These evidences suggest a complex interaction between TrkA, p75, and Aβ, whose exact cellular mechanisms remain still elusive. Here, we provide a general overview on the current knowledge on NGF and APP interplay, focusing on the events that mediate NGF signalling impairment, and, mostly, on the role of APP Tyrosine 682 phosphorylation whose absence in APPY682G mice impairs APP/TrkA interaction and leads to cholinergicneurodegeneration.