ArticleProceedings of the National Academy of Sciences of the United States of America2023
Slingshot homolog-1-mediated Nrf2 sequestration tips the balance from neuroprotection to neurodegeneration in Alzheimer's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- CHCHD2 mitigates age-associated proteostatic collapse by maintaining homeostasis of the mitochondria-lysosome axis.Acta neuropathologica · 2026Article
- Advances in nano-TCM for Alzheimer's disease: lipid-based carriers integrated with innovative delivery strategies.Journal of nanobiotechnology · 2026Review
- Ubiquitin-specific peptidase-19 links TDP-43 aggregation to ER stress.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Molecular and cellular processes connecting type 2 diabetes to Alzheimer's disease, focusing on oxidative stress, metabolic dysfunction, and neurodegeneration.Genetics and molecular biology · 2026Article
- Role of NRF2 in Electroacupuncture's Effects on Postoperative Cognitive Impairment in Rats.Neuropsychiatric disease and treatment · 2026Article
- A study to determine the effect of nano-selenium and thymoquinone on the Nrf2 gene expression in Alzheimer's disease.Future science OA · 2025Article
- Targeting macro- and micro-nutrient regulation of HNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Context-dependent regulatory variants in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Role of LIMK1-cofilin-actin axis in dendritic spine dynamics in Alzheimer's disease.Cell death & disease · 2025Review
- Deciphering novel mitochondrial signatures: multi-omics analysis uncovers cross-disease markers and oligodendrocyte pathways in Alzheimer's disease and glioblastoma.Frontiers in aging neuroscience · 2025Article
- Blood-based multivariate methylation risk score for cognitive impairment and dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Crystal Violet Selectively Detects Aβ Oligomers but Not Fibrils In Vitro and in Alzheimer's Disease Brain Tissue.Biomolecules · 2024Article
- Emerging small molecule inhibitors of Bach1 as therapeutic agents: Rationale, recent advances, and future perspectives.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Article
- Disruption of Mitophagy Flux through the PARL-PINK1 Pathway by CHCHD10 Mutations or CHCHD10 Depletion.Cells · 2023Article
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10 authors at 4 institutions in 1 country.
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Abstract
Oxidative damage in the brain is one of the earliest drivers of pathology in Alzheimer's disease (AD) and related dementias, both preceding and exacerbating clinical symptoms. In response to oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) is normally activated to protect the brain from oxidative damage. However, Nrf2-mediated defense against oxidative stress declines in AD, rendering the brain increasingly vulnerable to oxidative damage. Although this phenomenon has long been recognized, its mechanistic basis has been a mystery. Here, we demonstrate through in vitro and in vivo models, as well as human AD brain tissue, that Slingshot homolog-1 (SSH1) drives this effect by acting as a counterweight to neuroprotective Nrf2 in response to oxidative stress and disease. Specifically, oxidative stress-activated SSH1 suppresses nuclear Nrf2 signaling by sequestering Nrf2 complexes on actin filaments and augmenting Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 interaction, independently of SSH1 phosphatase activity. We also show that
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.