Abstract
IntroductionThe Notch signalling pathway regulates neuronal survival. It has some similarities with the APP signalling pathway, and competes with the latter for α- and γ-secretase proteolytic complexes. The objective of this study was to study the Notch signalling pathway in the hippocampi of patients with motor neuron disease.MethodsWe 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 ConclusionLow NICD expression suggests Notch signalling pathway inactivation in neurons. Inactivation of the pathway despite increased Notch1 expression is associated with a lack of α-secretase expression. We observed increased β-secretase expression associated with activation of the amyloid cascade of APP, leading to increases in amyloid-β 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.
Highlights
The Notch signalling pathway regulates neuronal survival
Inactivation of the Notch signalling pathway is an important factor in decreased neurogenic response in the hippocampi of patients with amyotrophic lateral sclerosis
In patients labelling was heterogeneous in all hippocampal areas, being more evident in granular neurons and remarkable in CA1, CA3, the polymorphic layer of CA4, and the subgranular zone (SGZ); Notch1 expression was observed in neurons and to a lesser extent in astrocytes and neuronal processes, following a slight synaptic pattern in CA1 and in capillary walls (Figure 1)
Summary
The Notch signalling pathway regulates neuronal survival. It has some similarities with the APP signalling pathway, and competes with the latter for α- and γ-secretase proteolytic complexes. The objective of this study was to study the Notch signalling pathway in the hippocampi of patients with motor neuron disease. The Notch signalling pathway regulates cell migration and growth, synaptic plasticity, and neuronal survival (Ables et al, 2011). There is an evident parallel between the Notch and amyloid precursor protein (APP) signalling pathways, which compete for proteolytic complexes; an association between both pathways has been suggested. It has been suggested that Notch participates in olfactory function (Brai et al, 2014), which is impaired in patients with Alzheimer disease (AD) (Berezovska et al, 1998; Moehlmann et al, 2002; Brai et al, 2016) and in experimental models of
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