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Repurposing niclosamide in mouse models of amyotrophic lateral sclerosis

ABSTRACT: Repurposing niclosamide in mouse models of amyotrophic lateral sclerosis

PROVIDER: PRJNA1047112 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27006132.fastq.gz	Fastqsanger.gz
	SRR27006133.fastq.gz	Fastqsanger.gz
	SRR27006134.fastq.gz	Fastqsanger.gz
	SRR27006135.fastq.gz	Fastqsanger.gz
	SRR27006136.fastq.gz	Fastqsanger.gz

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Repurposing niclosamide in mouse models of amyotrophic lateral sclerosis

Project description:ALS is a complex neurodegenerative disease influenced by genetic, epigenetic, and environmental factors, resulting in dysfunction in cellular and molecular pathways. The limited efficacy of current treatments highlights the need for combination therapies targeting multiple aspects of the disease. Niclosamide, an anthelminthic drug listed as an essential medicine, has been repurposed in clinical trials due to its anti-inflammatory and anti-fibrotic properties. Niclosamide can inhibit various molecular pathways (such as STAT3 and mTOR) that are dysregulated in ALS, suggesting its potential to disrupt these altered mechanisms associated with the pathology. Our recent findings have demonstrated that niclosamide can effectively inhibit inflammatory and fibrotic molecular pathways in ALS models. We administered niclosamide intraperitoneally to two transgenic murine models, FUS and SOD1-G93A mice, which replicate key pathologies and biological processes of ALS. The treatment was initiated at the onset of symptoms, and we assessed the progression of the disease by neurological scores, rotarod and grip tests, as well as monitoring survival. Additionally, we examined the effects of the treatment on spinal cord and muscle degeneration in the treated mice. In both models, the administration of niclosamide resulted in a slowdown of disease progression, an increase in survival rates, and an improvement in tissue pathology. This was characterized by a reduction in gliosis, motor neuron loss, muscle atrophy, and inflammatory markers. Based on these results, our findings demonstrate that niclosamide can impact multiple pathways involved in ALS. This multi-targeted approach leads to a slowdown in the progression of the disease, thereby positioning niclosamide as a promising candidate for repurposing in the treatment of ALS.

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