Small molecule targeting long noncoding RNA GAS5 administered intranasally improves neuronal insulin signaling and decreases neuroinflammation in an aged mouse model

Shifts in normal aging set stage for neurodegeneration and dementia affecting 1 in 10 adults. The study demonstrates that lncRNA GAS5 is decreased in aged and Alzheimer’s disease brain. The role and targets of lncRNA GAS5 in the aging brain were elucidated using a GAS5-targeting small molecule NPC86...

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Published inScientific reports Vol. 13; no. 1; p. 317
Main Authors Patel, Rekha S., Lui, Ashley, Hudson, Charles, Moss, Lauren, Sparks, Robert P., Hill, Shannon E., Shi, Yan, Cai, Jianfeng, Blair, Laura J., Bickford, Paula C., Patel, Niketa A.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 06.01.2023
Nature Publishing Group
Nature Portfolio
Subjects
631/337
631/337/384
692/4017
692/700/1518
Age
Aging
Alzheimer's disease
Animals
Brain research
Cognition & reasoning
Dementia
Dementia disorders
Diabetes
Disease Models, Animal
Gene expression
Humanities and Social Sciences
Inflammation
Insulin
Insulin - metabolism
Insulin resistance
Kinases
Mice
MicroRNAs - genetics
Molecular dynamics
multidisciplinary
Neurodegeneration
Neurodegenerative diseases
Neuroinflammatory Diseases
Neurons - metabolism
Non-coding RNA
Phosphorylation
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
Science
Science (multidisciplinary)
Signal Transduction
Tau protein
Toll-like receptors
Transcriptomics
Veterans
Online AccessGet full text

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Abstract Shifts in normal aging set stage for neurodegeneration and dementia affecting 1 in 10 adults. The study demonstrates that lncRNA GAS5 is decreased in aged and Alzheimer’s disease brain. The role and targets of lncRNA GAS5 in the aging brain were elucidated using a GAS5-targeting small molecule NPC86, a frontier in lncRNA-targeting therapeutic. Robust techniques such as molecular dynamics simulation of NPC86 binding to GAS5, in vitro functional assays demonstrating that GAS5 regulates insulin signaling, neuronal survival, phosphorylation of tau, and neuroinflammation via toll-like receptors support the role of GAS5 in maintaining healthy neurons. The study demonstrates the safety and efficacy of intranasal NPC86 treatment in aged mice to improve cellular functions with transcriptomic analysis in response to NPC86. In summary, the study demonstrates that GAS5 contributes to pathways associated with neurodegeneration and NPC86 has tremendous therapeutic potential to prevent the advent of neurodegenerative diseases and dementias.
AbstractList Shifts in normal aging set stage for neurodegeneration and dementia affecting 1 in 10 adults. The study demonstrates that lncRNA GAS5 is decreased in aged and Alzheimer’s disease brain. The role and targets of lncRNA GAS5 in the aging brain were elucidated using a GAS5-targeting small molecule NPC86, a frontier in lncRNA-targeting therapeutic. Robust techniques such as molecular dynamics simulation of NPC86 binding to GAS5, in vitro functional assays demonstrating that GAS5 regulates insulin signaling, neuronal survival, phosphorylation of tau, and neuroinflammation via toll-like receptors support the role of GAS5 in maintaining healthy neurons. The study demonstrates the safety and efficacy of intranasal NPC86 treatment in aged mice to improve cellular functions with transcriptomic analysis in response to NPC86. In summary, the study demonstrates that GAS5 contributes to pathways associated with neurodegeneration and NPC86 has tremendous therapeutic potential to prevent the advent of neurodegenerative diseases and dementias.
Abstract Shifts in normal aging set stage for neurodegeneration and dementia affecting 1 in 10 adults. The study demonstrates that lncRNA GAS5 is decreased in aged and Alzheimer’s disease brain. The role and targets of lncRNA GAS5 in the aging brain were elucidated using a GAS5-targeting small molecule NPC86, a frontier in lncRNA-targeting therapeutic. Robust techniques such as molecular dynamics simulation of NPC86 binding to GAS5, in vitro functional assays demonstrating that GAS5 regulates insulin signaling, neuronal survival, phosphorylation of tau, and neuroinflammation via toll-like receptors support the role of GAS5 in maintaining healthy neurons. The study demonstrates the safety and efficacy of intranasal NPC86 treatment in aged mice to improve cellular functions with transcriptomic analysis in response to NPC86. In summary, the study demonstrates that GAS5 contributes to pathways associated with neurodegeneration and NPC86 has tremendous therapeutic potential to prevent the advent of neurodegenerative diseases and dementias.
Abstract Shifts in normal aging set stage for neurodegeneration and dementia affecting 1 in 10 adults. The study demonstrates that lncRNA GAS5 is decreased in aged and Alzheimer’s disease brain. The role and targets of lncRNA GAS5 in the aging brain were elucidated using a GAS5-targeting small molecule NPC86, a frontier in lncRNA-targeting therapeutic. Robust techniques such as molecular dynamics simulation of NPC86 binding to GAS5, in vitro functional assays demonstrating that GAS5 regulates insulin signaling, neuronal survival, phosphorylation of tau, and neuroinflammation via toll-like receptors support the role of GAS5 in maintaining healthy neurons. The study demonstrates the safety and efficacy of intranasal NPC86 treatment in aged mice to improve cellular functions with transcriptomic analysis in response to NPC86. In summary, the study demonstrates that GAS5 contributes to pathways associated with neurodegeneration and NPC86 has tremendous therapeutic potential to prevent the advent of neurodegenerative diseases and dementias.
ArticleNumber 317
Author Hudson, Charles
Blair, Laura J.
Patel, Rekha S.
Bickford, Paula C.
Hill, Shannon E.
Lui, Ashley
Moss, Lauren
Sparks, Robert P.
Shi, Yan
Cai, Jianfeng
Patel, Niketa A.
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Snippet Shifts in normal aging set stage for neurodegeneration and dementia affecting 1 in 10 adults. The study demonstrates that lncRNA GAS5 is decreased in aged and...
Abstract Shifts in normal aging set stage for neurodegeneration and dementia affecting 1 in 10 adults. The study demonstrates that lncRNA GAS5 is decreased in...
Abstract Shifts in normal aging set stage for neurodegeneration and dementia affecting 1 in 10 adults. The study demonstrates that lncRNA GAS5 is decreased in...
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SubjectTerms 631/337
631/337/384
692/4017
692/700/1518
Age
Aging
Alzheimer's disease
Animals
Brain research
Cognition & reasoning
Dementia
Dementia disorders
Diabetes
Disease Models, Animal
Gene expression
Humanities and Social Sciences
Inflammation
Insulin
Insulin - metabolism
Insulin resistance
Kinases
Mice
MicroRNAs - genetics
Molecular dynamics
multidisciplinary
Neurodegeneration
Neurodegenerative diseases
Neuroinflammatory Diseases
Neurons - metabolism
Non-coding RNA
Phosphorylation
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
Science
Science (multidisciplinary)
Signal Transduction
Tau protein
Toll-like receptors
Transcriptomics
Veterans
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Title Small molecule targeting long noncoding RNA GAS5 administered intranasally improves neuronal insulin signaling and decreases neuroinflammation in an aged mouse model
URI https://link.springer.com/article/10.1038/s41598-022-27126-6
https://www.ncbi.nlm.nih.gov/pubmed/36609440
https://www.proquest.com/docview/2761462029
https://search.proquest.com/docview/2761985848
https://pubmed.ncbi.nlm.nih.gov/PMC9822944
https://doaj.org/article/7e1cfc1749fc453bb56dae844a64cc03
Volume 13
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