aFGF Promotes Neurite Growth by Regulating GSK3β-CRMP2 Signaling Pathway in Cortical Neurons Damaged by Amyloid-β.

Abstract

Glycogen synthase kinase 3β (GSK3β) 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 GSK3β through the PI3K/Akt signaling pathway. We found that aFGF14-154 markedly increased the average length of neurites in neurons damaged by amyloid-β (Aβ), and this promoting effect was blocked by GSK3β inhibitor. It is still unknown which downstream substrates of GSK3β are related to the neurite growth facilitated by aFGF14-154. The downstream substrates interacting with GSK3β 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 GSK3β, which is involved in the axon formation and neuron regeneration by regulating microtubule reorganization. aFGF14-154 increased the phosphorylation of GSK3β (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 Aβ injury. These results highlight the important role of CRMP2 and its phosphorylation through GSK3β in the effect that aFGF14-154 promoted the growth of neurite damaged by Aβ.

• Authors: Qin Cao, Tian Meng, Jianhui Man, Dong Peng, Hongxia Chen, Qi Xiang, Zhijian Su, Qihao Zhang, Yadong Huang
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 72 Issue 1 Pg. 97-109 ( 2019) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 31561361 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Intercellular Signaling Peptides and Proteins
• Nerve Tissue Proteins
• Peptide Fragments
• amyloid beta-protein (1-42)
• collapsin response mediator protein-2
• Fibroblast Growth Factor 1
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, rat

Topics

• Amyloid beta-Peptides (toxicity)
• Animals
• Animals, Newborn
• Cells, Cultured
• Cerebral Cortex (cytology, drug effects, metabolism)
• Fibroblast Growth Factor 1 (pharmacology)
• Glycogen Synthase Kinase 3 beta (genetics, metabolism)
• Humans
• Intercellular Signaling Peptides and Proteins (deficiency, genetics)
• Nerve Tissue Proteins (deficiency, genetics)
• Neurites (drug effects, metabolism)
• Neurons (drug effects, metabolism)
• Peptide Fragments (toxicity)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects, physiology)