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WIREs Dev Biol
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The Notch pathway in CNS homeostasis and neurodegeneration

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Abstract The role of the Notch signaling pathway in neural development has been well established over many years. More recent studies, however, have demonstrated that Notch continues to be expressed and active throughout adulthood in many areas of the central nervous system. Notch signals have been implicated in adult neurogenesis, memory formation, and synaptic plasticity in the adult organism, as well as linked to acute brain trauma and chronic neurodegenerative conditions. NOTCH3 mutations are responsible for the most common form of hereditary stroke, the progressive disorder cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Notch has also been associated with several progressive neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Although numerous studies link Notch activity with CNS homeostasis and neurodegenerative diseases, the data thus far are primarily correlative, rather than functional. Nevertheless, the evidence for Notch pathway activity in specific neural cellular contexts is strong, and certainly intriguing, and points to the possibility that the pathway carries therapeutic promise. This article is categorized under: Nervous System Development > Flies Signaling Pathways > Cell Fate Signaling Nervous System Development > Vertebrates: General Principles
Notch signaling mediates outgrowth of post‐mitotic neurons. (a) Neurite extension in cortical neurons is normally inhibited upon contact with a neighboring neuron. (b) When Notch signaling is inhibited cell‐autonomously via overexpression of a negative Notch regulator (e.g., Deltex or Numb‐like), contact‐mediated inhibition is relieved and neurite extension occurs (adapted from Sestan et al., )
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Nervous System Development > Vertebrates: General Principles
Nervous System Development > Flies
Signaling Pathways > Cell Fate Signaling