Circadian restoration of metabolic homeostasis as a novel strategy to counteract ALS disease
| Componente | Categoria |
|---|---|
| Antonio Musaro' | Componenti strutturati del gruppo di ricerca |
| Emanuele Rizzuto | Componenti strutturati del gruppo di ricerca |
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with motor neuron degeneration, muscle atrophy and paralysis and for which no effective therapy is known.
The pathogenesis of ALS is not completely understood and while much controversy remains about its molecular and biochemical biology, there is increasing consensus that multiple mechanisms of injury converge as the disease progress.
Mounting evidence suggest that alterations of body metabolic homeostasis represent a crucial event in ALS onset or even a possible trigger of the pathology.
The hypothalamus and the Superchiasmatic nucleus (SNC) control circadian rhythm and metabolic changes, both of which are severely compromised in neurodegenerative disorders, such as ALS. The SNC synchronizes downstream peripheral clock, including the muscle one, to preserve tissue homeostasis, according to a functional hierarchy in response to environmental cues.
Here we propose to analyze the circadian rhythm in the hypothalamus and skeletal muscle of SOD1G93A mice, in pre-symptomatic phase and during disease progression, in order to verify whether the restoration of circadian metabolic homeostasis could represent a novel strategy to delay onset and attenuate disease progression.