title: Cytoskeletal protection: acting on notch to prevent neuronal dysfunction.
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.
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Sara Anna
authors.initials: SA
authors.lastname: Bonini
authors.forename: Giulia
authors.initials: G
authors.lastname: Ferrari-Toninelli
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Maccarinelli
authors.forename: Paola
authors.initials: P
authors.lastname: Bettinsoli
authors.forename: Mery
authors.initials: M
authors.lastname: Montinaro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Memo
mesh_terms: D001921:Brain / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051880:Receptors, Notch