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Drug repositioning in neurodegeneration: An overview of the use of ambroxol in neurodegenerative diseases
- Source :
- European Journal of Pharmacology, European Journal of Pharmacology, 2020, 884, pp.173446. ⟨10.1016/j.ejphar.2020.173446⟩, European Journal of Pharmacology, Elsevier, 2020, 884, pp.173446. ⟨10.1016/j.ejphar.2020.173446⟩
- Publication Year :
- 2020
- Publisher :
- HAL CCSD, 2020.
-
Abstract
- International audience; Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults. While it is primarily characterized by the death of upper and lower motor neurons, there is a significant metabolic component involved in the progression of the disease. Two-thirds of ALS patients have metabolic alterations that are associated with the severity of symptoms. In ALS, as in other neurodegenerative diseases, the metabolism of glycosphingolipids, a class of complex lipids, is strongly dysregulated. We therefore assume that this pathway constitutes an interesting avenue for therapeutic approaches. We have shown that the glucosylceramide degrading enzyme, glucocerebrosidase (GBA) 2 is abnormally increased in the spinal cord of the SOD1G86R mouse model of ALS. Ambroxol, a chaperone molecule that inhibits GBA2, has been shown to have beneficial effects by slowing the development of the disease in SOD1G86R mice. Currently used in clinical trials for Parkinson's and Gaucher disease, ambroxol could be considered as a promising therapeutic treatment for ALS.
- Subjects :
- 0301 basic medicine
[SDV]Life Sciences [q-bio]
Ambroxol
GBA2
Disease
Bioinformatics
Neurodegenerative disease
MESH: Glucosylceramidase
MESH: Nerve Degeneration
MESH: Spinal Cord
Superoxide Dismutase-1
0302 clinical medicine
Medicine
MESH: Animals
Enzyme Inhibitors
Amyotrophic lateral sclerosis
MESH: Amyotrophic Lateral Sclerosis
MESH: Superoxide Dismutase-1
beta-Glucosidase
Neurodegeneration
MESH: Neuroprotective Agents
3. Good health
[SDV] Life Sciences [q-bio]
Drug repositioning
Neuroprotective Agents
medicine.anatomical_structure
Spinal Cord
MESH: Enzyme Inhibitors
Disease Progression
Glucosylceramidase
MESH: Disease Progression
MESH: Drug Repositioning
medicine.drug
MESH: Mutation
03 medical and health sciences
Animals
Humans
Pharmacology
MESH: Ambroxol
MESH: Humans
business.industry
Amyotrophic Lateral Sclerosis
Drug Repositioning
MESH: beta-Glucosidase
Motor neuron
medicine.disease
Spinal cord
Disease Models, Animal
030104 developmental biology
Mutation
Nerve Degeneration
Glucosylceramide
ALS
MESH: Disease Models, Animal
business
Glucocerebrosidase
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 00142999
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmacology, European Journal of Pharmacology, 2020, 884, pp.173446. ⟨10.1016/j.ejphar.2020.173446⟩, European Journal of Pharmacology, Elsevier, 2020, 884, pp.173446. ⟨10.1016/j.ejphar.2020.173446⟩
- Accession number :
- edsair.doi.dedup.....5d5d2c9bf5526c8fda5405cf68e3ac9c