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- Title
Cytoskeletal Protection: Acting on Notch to Prevent Neuronal Dysfunction.
- Authors
Bonini, Sara Anna; Ferrari-Toninelli, Giulia; Maccarinelli, Giuseppina; Bettinsoli, Paola; Montinaro, Mery; Memo, Maurizio
- Abstract
Functional and structural plasticity is a fundamental property of the brain involving chemical, electrical, molecular and cellular responses and leading to reorganization of connections within a brain region and/or between brain regions. The Notch pathway has been recognized as one of the main contributors in regulating neural development and has been proposed as a key mediator in neuroplasticity. We supported this concept, demonstrating that Notch plays a role in determining the only possible 'cell fate' decisions in post-mitotic mature neurons: synaptic remodelling or neurite extension/retraction. We demonstrated that Notch pathway activation causes a decrease in neurite branching and a loss of varicosities, with consequent reduction in the release of neurotransmitters. Furthermore, in dysfunctional neurons that present Notch pathway hyper-activation, neuronal morphology was reverted by Notch-inhibiting agents. Potentially, a better understanding of the molecular events participating in neuroplasticity may provide relevant information for innovative therapeutic approaches in a variety of neurological disorders. Hence, we propose a Notch-signalling fine-tuned manipulation as a novel approach to modulate neuronal cytoskeleton plasticity in order to prevent dysfunctional structural plasticity in neurodegenerative diseases. © 2013 S. Karger AG, Basel
- Subjects
CYTOSKELETAL proteins; NOTCH proteins; NEURAL physiology; NEUROPLASTICITY; BRAIN physiology; NEURON development; NEUROTRANSMITTERS
- Publication
Neurodegenerative Diseases, 2014, Vol 13, Issue 2/3, p93
- ISSN
1660-2854
- Publication type
Article
- DOI
10.1159/000354230