Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Raptor downregulation rescues neuronal phenotypes in mouse models of Tuberous Sclerosis Complex Tuberous Sclerosis Complex (TSC) is a neurodevelopmental disorder caused by mutations in the TSC1 or TSC2 genes, which encode proteins that negatively regulate mTOR complex 1 (mTORC1) signaling. Current treatment strategies focus on mTOR inhibition with rapamycin and its derivatives. While effective at improving some aspects of TSC, chronic rapamycin inhibits both mTORC1 and mTORC2 and is associated with systemic side-effects. It is currently unknown which mTOR complex is most relevant for TSC-related brain phenotypes. Here we used genetic strategies to selectively reduce neuronal mTORC1 or mTORC2 activity in mouse models of TSC. We find that reduction of the mTORC1 component Raptor, but not the mTORC2 component Rictor, rebalanced mTOR signaling in Tsc1 knock-out neurons. Raptor reduction was sufficient to improve several TSC-related phenotypes including neuronal hypertrophy, macrocephaly, impaired myelination, network hyperactivity, and premature mortality. Raptor downregulation represents a promising potential therapeutic intervention for the neurological manifestations of TSC.
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The categories of this paper are: plant
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The categories of this paper are: ecology
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The categories of this paper are: education
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The categories of this paper are: scientific
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The categories of this paper are: toxicology
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The categories of this paper are: communication
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The categories of this paper are: pharmacology
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The categories of this paper are: bioinformatics
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The categories of this paper are: systems
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The categories of this paper are: physiology
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The categories of this paper are: molecular
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The categories of this paper are: biophysics
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The categories of this paper are: cancer
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The categories of this paper are: behavior
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The categories of this paper are: bioengineering
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The categories of this paper are: biochemistry