Notch Signalling in the Hippocampus of Patients With Motor Neuron Disease.

hippocampal neurogenesis ADAM10 ADAM17 ALS APP BACE1 NICD Notch

Journal

Frontiers in neuroscience
ISSN: 1662-4548
Titre abrégé: Front Neurosci
Pays: Switzerland
ID NLM: 101478481

Informations de publication

Date de publication:
2019
Historique:
received: 10 12 2018
accepted: 15 03 2019
entrez: 27 4 2019
pubmed: 27 4 2019
medline: 27 4 2019
Statut: epublish

Résumé

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. 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. Low 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.

Identifiants

pubmed: 31024234
doi: 10.3389/fnins.2019.00302
pmc: PMC6460507
doi:

Types de publication

Journal Article

Langues

eng

Pagination

302

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Auteurs

Ulises Gómez-Pinedo (U)

Laboratory of Neurobiology, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain.

Lucía Galán (L)

Department of Neurology, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain.

Jordi A Matías-Guiu (JA)

Department of Neurology, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain.

Vanesa Pytel (V)

Laboratory of Neurobiology, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain.
Department of Neurology, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain.

Teresa Moreno (T)

Department of Neurology, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain.

Antonio Guerrero-Sola (A)

Department of Neurology, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain.

Jorge Matías-Guiu (J)

Laboratory of Neurobiology, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain.
Department of Neurology, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain.

Classifications MeSH