Cytoskeletal protection: acting on notch to prevent neuronal dysfunction

• Published in: Neuro-degenerative diseases Vol. 13; no. 2-3; p. 93
• Main Authors: Bonini, Sara Anna, Ferrari-Toninelli, Giulia, Maccarinelli, Giuseppina, Bettinsoli, Paola, Montinaro, Mery, Memo, Maurizio
• Format: Journal Article
• Language: English
• Published: Switzerland 2014
• Subjects: Brain - metabolism; Cytoskeleton - metabolism; Humans; Neurodegenerative Diseases - metabolism; Neuronal Plasticity - physiology; Neurons - metabolism; Receptors, Notch - metabolism; Signal Transduction - physiology
• ISSN: 1660-2862
• DOI: 10.1159/000354230

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.