Astrocyte-derived Jagged-1 mitigates deleterious Notch signaling in amyotrophic lateral sclerosis

Neurobiology of Disease
Annelies NonnemanWim Robberecht

Abstract

Amyotrophic lateral sclerosis (ALS) is a late-onset devastating degenerative disease mainly affecting motor neurons. Motor neuron degeneration is accompanied and aggravated by oligodendroglial pathology and the presence of reactive astrocytes and microglia. We studied the role of the Notch signaling pathway in ALS, as it is implicated in several processes that may contribute to this disease, including axonal retraction, microgliosis, astrocytosis, oligodendrocyte precursor cell proliferation and differentiation, and cell death. We observed abnormal activation of the Notch signaling pathway in the spinal cord of SOD1G93A mice, a well-established model for ALS, as well as in the spinal cord of patients with sporadic ALS (sALS). This increased activation was particularly evident in reactive GFAP-positive astrocytes. In addition, one of the main Notch ligands, Jagged-1, was ectopically expressed in reactive astrocytes in spinal cord from ALS mice and patients, but absent in resting astrocytes. Astrocyte-specific inactivation of Jagged-1 in presymptomatic SOD1G93A mice further exacerbated the activation of the Notch signaling pathway and aggravated the course of the disease in these animals without affecting disease onset. These dat...Continue Reading

Citations

Sep 11, 2019·Wiley Interdisciplinary Reviews. Developmental Biology·Diana M HoAngeliki Louvi
Jul 8, 2020·Biomolecules·Jose L SalazarShinya Yamamoto
Apr 27, 2019·Frontiers in Neuroscience·Ulises Gómez-PinedoJorge Matías-Guiu
Dec 12, 2019·Frontiers in Neurology·Mariana Dutra BritoTatiana Rosado Rosenstock
Apr 10, 2019·Cell Death Discovery·Estefania Acaz-FonsecaMaria-Angeles Arevalo
Jan 16, 2021·Experimental & Molecular Medicine·Jinyoung Lee, Yongcheol Cho
Jun 11, 2021·Developmental and Comparative Immunology·Hui ZhouDefu Yao

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