aFGF Promotes Neurite Growth by Regulating GSK3?-CRMP2 Signaling Pathway in Cortical Neurons Damaged by Amyloid-?.

Glycogen synthase kinase 3? (GSK3?) is a key component of pathogenesis in Alzheimer's disease, and its inhibitors can restore cognitive function as therapeutic interventions in neurodegenerative diseases. The previous studies showed that acidic fibroblast growth factor (aFGF) could increase the phosphorylation of GSK3? through the PI3K/Akt signaling pathway. We found ...
that aFGF14-154 markedly increased the average length of neurites in neurons damaged by amyloid-? (A?), and this promoting effect was blocked by GSK3? inhibitor. It is still unknown which downstream substrates of GSK3? are related to the neurite growth facilitated by aFGF14-154. The downstream substrates interacting with GSK3? were screened by co-immunoprecipitation and LTQ-Orbitrap proteomics technology in our study. Collapsin response mediator protein 2 (CRMP2) has been identified as a protein interacting with GSK3?, which is involved in the axon formation and neuron regeneration by regulating microtubule reorganization. aFGF14-154 increased the phosphorylation of GSK3? (Ser9) to inhibit its activity, then was followed by a low phosphorylation level of CRMP2 (Thr514), which led to the neurite growth. The knockdown of CRMP2 blocked the rescue of aFGF14-154 with broken neurites and shrunken cell bodies in neurons with A? injury. These results highlight the important role of CRMP2 and its phosphorylation through GSK3? in the effect that aFGF14-154 promoted the growth of neurite damaged by A?.
Mesh Terms:
Amyloid beta-Peptides, Animals, Animals, Newborn, Cells, Cultured, Cerebral Cortex, Fibroblast Growth Factor 1, Glycogen Synthase Kinase 3 beta, Humans, Intercellular Signaling Peptides and Proteins, Nerve Tissue Proteins, Neurites, Neurons, Peptide Fragments, Rats, Rats, Sprague-Dawley, Signal Transduction
J Alzheimers Dis
Date: Sep. 29, 2019
Download Curated Data For This Publication
226496
Switch View:
  • Interactions 2