Author/Editor		Vicario, Nunzio; Spitale, Federica M.; Tibullo, Daniele; Giallongo, Cesarina; Amorini, Angela M. A; Scandura, Grazia; Spoto, Graziana; Saab, Miriam W.; D'Aprile, Simona; Zorec, Robert
Title		Clobetasol promotes neuromuscular plasticity in miceafter motoneuronal loss via sonic hedgehog signaling,immunomodulation and metabolic rebalancing
Type		članek
Vol. and No.		, št. Vol. 12
Publication year		2021
Volume		str. 1-13
ISSN		2041-4889 - Cell death & disease
Language		eng
Abstract		Motoneuronal loss is the main feature of amyotrophic lateral sclerosis, although pathogenesis is extremely complex involving bothneural and muscle cells. In order to translationally engage the sonic hedgehog pathway, which is a promising target for neuralregeneration, recent studies have reported on the neuroprotective effects of clobetasol, an FDA-approved glucocorticoid, able toactivate this pathway via smoothened. Herein we sought to examine functional, cellular, and metabolic effects of clobetasol in aneurotoxic mouse model of spinal motoneuronal loss. We found that clobetasol reduces muscle denervation and motorimpairments in part by restoring sonic hedgehog signaling and supporting spinal plasticity. These effects were coupled withreduced pro-inflammatory microglia and reactive astrogliosis, reduced muscle atrophy, and support of mitochondrial integrity andmetabolism. Our results suggest that clobetasol stimulates a series of compensatory processes and therefore represents atranslational approach for intractable denervating and neurodegenerative disorders.
Keywords		amyotrophic lateral sclerosis effects of clobetasol neurodegenerative disorders amiotrofična lateralna skleroza učinki klobetazola nevrodegenerativne motnje