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PIKFYVE Inhibition Mitigates Disease in Models of Diverse Forms of ALS [1]

ABSTRACT: PIKFYVE Inhibition Mitigates Disease in Models of Diverse Forms of ALS [1]

PROVIDER: PRJNA912588 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22746374.fastq.gz	Fastqsanger.gz
	SRR22746375.fastq.gz	Fastqsanger.gz
	SRR22746376.fastq.gz	Fastqsanger.gz
	SRR22746377.fastq.gz	Fastqsanger.gz
	SRR22746378.fastq.gz	Fastqsanger.gz

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PIKFYVE Inhibition Mitigates Disease in Models of Diverse Forms of ALS

Project description:PIKFYVE Inhibition Mitigates Disease in Models of Diverse Forms of ALS

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PIKFYVE Inhibition Mitigates Disease in Models of Diverse Forms of ALS [2]

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PIKFYVE Inhibition Mitigates Disease in Models of Diverse Forms of ALS [2]

Project description:RNA sequencing analysis of human iPSC-derived motor neurons generated from two C9ORF72 ALS/FTD patient lines, treated with negative control ASO (NC ASO) or PIKFYVE ASO. The goal of this study is to evaluate the effect of PIKFYVE suppression in rescuing ALS motor neuron degeneration.

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PIKFYVE Inhibition Mitigates Disease in Models of Diverse Forms of ALS [1]

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SYF2 Suppression Mitigates Neurodegeneration in Models of Diverse Forms of ALS

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PIKFYVE inhibition mitigates disease in models of diverse forms of ALS.

Project description:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that results from many diverse genetic causes. Although therapeutics specifically targeting known causal mutations may rescue individual types of ALS, these approaches cannot treat most cases since they have unknown genetic etiology. Thus, there is a pressing need for therapeutic strategies that rescue multiple forms of ALS. Here, we show that pharmacological inhibition of PIKFYVE kinase activates an unconventional protein clearance mechanism involving exocytosis of aggregation-prone proteins. Reducing PIKFYVE activity ameliorates ALS pathology and extends survival of animal models and patient-derived motor neurons representing diverse forms of ALS including C9ORF72, TARDBP, FUS, and sporadic. These findings highlight a potential approach for mitigating ALS pathogenesis that does not require stimulating macroautophagy or the ubiquitin-proteosome system.

| S-EPMC10062012 | biostudies-literature

PIKFYVE Inhibition Mitigates Disease in Models of Diverse Forms of ALS

Project description:This SuperSeries is composed of the SubSeries listed below.

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SYF2 Suppression Mitigates Neurodegeneration in Models of Diverse Forms of ALS

Project description:RNA sequencing analysis of human induced motor neurons generated from a C9ORF72 ALS patient line and its isogenic control, treated with siRNA targetting SYF2. The goal of this study is to evaluate the process of SYF2 suppression in rescuing ALS motor neuron degeneration.

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SYF2 suppression mitigates neurodegeneration in models of diverse forms of ALS.

Project description:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by many diverse genetic etiologies. Although therapeutics that specifically target causal mutations may rescue individual types of ALS, such approaches cannot treat most patients since they have unknown genetic etiology. Thus, there is a critical need for therapeutic strategies that rescue multiple forms of ALS. Here, we combine phenotypic chemical screening on a diverse cohort of ALS patient-derived neurons with bioinformatic analysis of large chemical and genetic perturbational datasets to identify broadly effective genetic targets for ALS. We show that suppressing the gene-encoding, spliceosome-associated factor SYF2 alleviates TDP-43 aggregation and mislocalization, improves TDP-43 activity, and rescues C9ORF72 and causes sporadic ALS neuron survival. Moreover, Syf2 suppression ameliorates neurodegeneration, neuromuscular junction loss, and motor dysfunction in TDP-43 mice. Thus, suppression of spliceosome-associated factors such as SYF2 may be a broadly effective therapeutic approach for ALS.

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Alveolar macrophage gene expression - PIKfyve knockout

Project description:comparison of Alveolar macrophge gene expression in wild type and PIKfyve ko We identifed gene that important for alveolar macrophage development

2017-03-01 | GSE93849 | GEO

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