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Death Induced by Survival gene Elimination (DISE) is correlated with neurotoxicity in Alzheimer's disease and aging

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE213138 | GEO | 2023/12/07

REPOSITORIES: GEO

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Death Induced by Survival gene Elimination (DISE) is correlated with neurotoxicity in Alzheimer's disease and aging

Project description:Analysis of RISC bound short (s)RNAs in various cell lines and mouse models of Alzheimer's disease and in human AD patients reveals a contribution of 6mer seed toxicity to the neurotoxicity associated with AD

2023-12-07 | GSE213129 | GEO

Death Induced by Survival gene Elimination (DISE) is correlated with neurotoxicity in Alzheimer's disease and aging

2023-12-07 | GSE213127 | GEO

Death Induced by Survival gene Elimination (DISE) is correlated with neurotoxicity in Alzheimer's disease and aging

2023-12-07 | GSE213121 | GEO

Death Induced by Survival gene Elimination (DISE) is correlated with neurotoxicity in Alzheimer's disease and aging

2023-12-07 | GSE213136 | GEO

Death Induced by Survival gene Elimination (DISE) is correlated with neurotoxicity in Alzheimer's disease and aging

2023-12-07 | GSE213134 | GEO

Death Induced by Survival gene Elimination (DISE) is correlated with neurotoxicity in Alzheimer's disease and aging

2023-12-07 | GSE213131 | GEO

Death Induced by Survival gene Elimination (DISE) is correlated with neurotoxicity in Alzheimer's disease and aging

2023-12-07 | GSE213130 | GEO

Death Induced by Survival gene Elimination (DISE) is correlated with neurotoxicity in Alzheimer's disease and aging

2023-12-07 | GSE213122 | GEO

Death Induced by Survival gene Elimination (DISE) is correlated with neurotoxicity in Alzheimer's disease and aging

2023-12-07 | GSE213137 | GEO

Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer's disease and aging.

Project description:Alzheimer's disease (AD) is characterized by progressive neurodegeneration, but the specific events that cause cell death remain poorly understood. Death Induced by Survival gene Elimination (DISE) is a cell death mechanism mediated by short (s) RNAs acting through the RNA-induced silencing complex (RISC). DISE is thus a form of RNA interference, in which G-rich 6mer seed sequences in the sRNAs (position 2-7) target hundreds of C-rich 6mer seed matches in genes essential for cell survival, resulting in the activation of cell death pathways. Here, using Argonaute precipitation and RNAseq (Ago-RP-Seq), we analyze RISC-bound sRNAs to quantify 6mer seed toxicity in several model systems. In mouse AD models and aging brain, in induced pluripotent stem cell-derived neurons from AD patients, and in cells exposed to Aβ42 oligomers, RISC-bound sRNAs show a shift to more toxic 6mer seeds compared to controls. In contrast, in brains of "SuperAgers", humans over age 80 who have superior memory performance, RISC-bound sRNAs are shifted to more nontoxic 6mer seeds. Cells depleted of nontoxic sRNAs are sensitized to Aβ42-induced cell death, and reintroducing nontoxic RNAs is protective. Altogether, the correlation between DISE and Aβ42 toxicity suggests that increasing the levels of nontoxic miRNAs in the brain or blocking the activity of toxic RISC-bound sRNAs could ameliorate neurodegeneration.

| S-EPMC10796375 | biostudies-literature

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