Back to Search
Start Over
Clobetasol promotes neuromuscular plasticity in mice after motoneuronal loss via sonic hedgehog signaling, immunomodulation and metabolic rebalancing
- Source :
- Cell Death & Disease, Cell Death and Disease, Vol 12, Iss 7, Pp 1-13 (2021)
- Publication Year :
- 2021
- Publisher :
- Springer Nature, 2021.
-
Abstract
- Motoneuronal loss is the main feature of amyotrophic lateral sclerosis, although pathogenesis is extremely complex involving both neural and muscle cells. In order to translationally engage the sonic hedgehog pathway, which is a promising target for neural regeneration, recent studies have reported on the neuroprotective effects of clobetasol, an FDA-approved glucocorticoid, able to activate this pathway via smoothened. Herein we sought to examine functional, cellular, and metabolic effects of clobetasol in a neurotoxic mouse model of spinal motoneuronal loss. We found that clobetasol reduces muscle denervation and motor impairments in part by restoring sonic hedgehog signaling and supporting spinal plasticity. These effects were coupled with reduced pro-inflammatory microglia and reactive astrogliosis, reduced muscle atrophy, and support of mitochondrial integrity and metabolism. Our results suggest that clobetasol stimulates a series of compensatory processes and therefore represents a translational approach for intractable denervating and neurodegenerative disorders.
- Subjects :
- Male
Cancer Research
Physiology
129 Strain
Biochemistry
Mice
Databases, Genetic
Medicine
Myocyte
Motor Neurons
Neuronal Plasticity
Skeletal
Smoothened Receptor
Hedgehog signaling pathway
Muscle atrophy
Mitochondria
Astrogliosis
Neuroprotective Agents
Muscle
medicine.symptom
Inflammation Mediators
Signal Transduction
Cholera Toxin
Mice, 129 Strain
hedgehog
Immunology
Motor Activity
Neuroprotection
Article
Databases
Cellular and Molecular Neuroscience
smoothened
Genetic
Animals
Humans
Hedgehog Proteins
Muscle, Skeletal
Hedgehog
Glucocorticoids
Muscle Denervation
QH573-671
Animal
business.industry
Amyotrophic Lateral Sclerosis
Glial biology
Cell Biology
medicine.disease
Saporins
Spine
Mitochondria, Muscle
Disease Models, Animal
clobetasol
inflammation
Case-Control Studies
Disease Models
Diseases of the nervous system
Cytology
Smoothened
business
Energy Metabolism
Neuroscience
Open Field Test
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cell Death & Disease, Cell Death and Disease, Vol 12, Iss 7, Pp 1-13 (2021)
- Accession number :
- edsair.doi.dedup.....36418db7187bf323d52a6c3c731d3267