Cytoskeletal Protection: Acting on Notch to Prevent Neuronal Dysfunction.

Cytoskeletal Protection: Acting on Notch to Prevent Neuronal Dysfunction.
Neurodegener Dis. 2013 Sep 4;
Authors: Bonini SA, Ferrari-Toninelli G, Maccarinelli G, Bettinsoli P, Montinaro M, Memo M
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 ord...

Source: Neuro-Degenerative Diseases - September 4, 2013 Category: Neurology Authors: Bonini SA, Ferrari-Toninelli G, Maccarinelli G, Bettinsoli P, Montinaro M, Memo M Tags: Neurodegener Dis Source Type: research