ArticleAging cell2021
p38 MAPK-mediated loss of nuclear RNase III enzyme Drosha underlies amyloid beta-induced neuronal stress in Alzheimer's disease.
Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Rethinking Alzheimer's: novel miRNAs illuminate a disease beyond the brain.Molecular psychiatry · 2026Pooled it
- Roles of microRNAs in acute lung injury and acute respiratory distress syndrome: mechanisms and clinical potential.Frontiers in immunology · 2025Review
- pyPAGE: A framework for Addressing biases in gene-set enrichment analysis-A case study on Alzheimer's disease.PLoS computational biology · 2024Article
- Biomarker profiling to determine clinical impact of microRNAs in cognitive disorders.Scientific reports · 2024Article
- Maintaining Drosha expression with Cdk5 inhibitors as a potential therapeutic strategy for early intervention after TBI.Experimental & molecular medicine · 2024Article
- Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer's disease and aging.Nature communications · 2024Article
- PLK1 Regulates MicroRNA Biogenesis through Drosha Phosphorylation.International journal of molecular sciences · 2023Article
- The adaptive evolution of cancer driver genes.BMC genomics · 2023Article
- MicroRNAs and MAPKs: Evidence of These Molecular Interactions in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- MicroRNA biogenesis pathway alterations in aging.Extracellular vesicles and circulating nucleic acids · 2023Review
- Analyzing alternative splicing in Alzheimer's disease postmortem brain: a cell-level perspective.Frontiers in molecular neuroscience · 2023Article
- p38 MAPK-mediated loss of nuclear RNase III enzyme Drosha underlies amyloid beta-induced neuronal stress in Alzheimer's disease.Aging cell · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
MicroRNAs (miRNAs) are small noncoding RNAs ubiquitously expressed in the brain and regulate gene expression at the post-transcriptional level. The nuclear RNase III enzyme Drosha initiates the maturation process of miRNAs in the nucleus. Strong evidence suggests that dysregulation of miRNAs is involved in many neurological disorders including Alzheimer's disease (AD). Dysfunction of miRNA biogenesis components may be involved in the processes of those diseases. However, the role of Drosha in AD remains unknown. By using immunohistochemistry, biochemistry, and subcellular fractionation methods, we show here that the level of Drosha protein was significantly lower in the postmortem brain of human AD patients as well as in the transgenic rat model of AD. Interestingly, Drosha level was specifically reduced in neurons of the cortex and hippocampus but not in the cerebellum in the AD brain samples. In primary cortical neurons, amyloid-beta (Aβ) oligomers caused a p38 MAPK-dependent phosphorylation of Drosha, leading to its redistribution from the nucleus to the cytoplasm and a decrease in its level. This loss of Drosha function preceded Aβ-induced neuronal death. Importantly, inhibition of p38 MAPK activity or overexpression of Drosha protected neurons from Aβ oligomers-induced apoptosis. Taken together, these results establish a role for p38 MAPK-Drosha pathway in modulating neuronal viability under Aβ oligomers stress condition and implicate loss of Drosha as a key molecular change in the pathogenesis of AD.
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