期刊
FRONTIERS IN NEUROSCIENCE
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2019.00302
关键词
ALS; Notch; NICD; APP; ADAM10; ADAM17; BACE1; hippocampal neurogenesis
Introduction: The Notch signalling pathway regulates neuronal survival. It has some similarities with the APP signalling pathway, and competes with the latter for alpha- and gamma-secretase proteolytic complexes. The objective of this study was to study the Notch signalling pathway in the hippocampi of patients with motor neuron disease. Methods: We studied biological material from the autopsies of 12 patients with motor neuron disease and 4 controls. We analysed the molecular markers of the Notch and APP signalling pathways, TDP43, tau, and markers of neurogenesis. Results and Conclusion: Low NICD expression suggests Notch signalling pathway inactivation in neurons. Inactivation of the pathway despite increased Notch1 expression is associated with a lack of alpha-secretase expression. We observed increased beta-secretase expression associated with activation of the amyloid cascade of APP, leading to increases in amyloid-beta and AICD peptides and decreased levels of Fe65. Inactivation of the Notch signalling pathway is an important factor in decreased neurogenic response in the hippocampi of patients with amyotrophic lateral sclerosis.
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