Active project: HMGB1 and ALS
HMGB1 and ALS.
Role of HMGB1 in ALS disease progression
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of motor neurons that causes neuromuscular junction (NMJ) loss and skeletal muscle paralysis. Most studies have been directed to develop treatments that prevent death of motor neurons, with the goal of stopping the progression of muscle atrophy. However, recent data have shown that motor neuron loss may represent a consequence of primary modifications occurring in skeletal muscle. One hypothesis is that skeletal muscle controls NMJ and motor neuron survival by modulating retrograde signals required for innervation.
Recently it has been shown that microRNA 206 (miR206), is induced in skeletal muscle of a mouse model of ALS (SOD1G93A). miR206 not only promotes myogenic differentiation, but also favours innervation and NMJ formation in ALS through the activation of histone deacetylase 4 and fibroblast growth factor signaling pathways in skeletal muscle. Through this mechanism miR206 may counteracts the disease progression.
HMGB1 is a ubiquitous nuclear protein released following tissue damage. We recently demonstrated that extracellular HMGB1 is a potent regenerative cytokine: its delivery to skeletal and cardiac muscle following injury enhances regeneration by activating endogenous stem cells and promoting angiogenesis. Notably our preliminary results suggest that, in cardiac muscle, the regenerative effects occur through the activation of miR206 expression.
Based on these evidences, overall objective of this project is to investigate whether HMGB1 is a signalling molecule that, through the regulation of miR206 in the skeletal muscle, may counteract ALS symptoms modulating retrograde signalling pathways involved in motor neuron survival, axonal growth and NMJ maintenance.
Research Team:
Capogrossi Colognesi Maurizio
E mail capogrossi@idi.it
Curriculum and References
Project Progress
Year 1
Time extension:
