ArticleMolecular neurodegeneration2019
Autophagy protein NRBF2 has reduced expression in Alzheimer's brains and modulates memory and amyloid-beta homeostasis in mice.
Article in Molecular neurodegeneration, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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62 citing papers in PubMed, 95 citations in OpenAlex.
- Dihydromyricetin ameliorates cognitive dysfunction in SAMP8 mice via autophagy-mediated degradation of the NLRP3 inflammasome.Metabolic brain disease · 2026Article
- Roles of autophagy in brain homeostasis and disease.Nature neuroscience · 2026Review
- Bridging autophagy and endolysosomal dysfunction: Role of bridging integrator 1 in Alzheimer's disease.Neural regeneration research · 2026Article
- The Central Role of Neuronal Cell Death in Alzheimer's Disease Pathobiology.Biomedicines · 2026Review
- L-Leucine Upregulates Lysosomal Biogenesis and Autophagy to Lower Plaques in 5XFAD Mouse Model of Alzheimer's Disease.Journal of neurochemistry · 2026Article
- Transcriptomic and proteomic insights into progressive myoclonus epilepsy type 1.Disease models & mechanisms · 2026Article
- Nanotechnology-based targeted delivery strategies for the treatment of Alzheimer's disease.Nanoscale advances · 2026Review
- Sex- and brain region-specific gene expression in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Article
- Brain and circulating EV proteome signatures in schizophrenia as prognostic markers for age-related dementia.Acta neuropathologica communications · 2026Article
- The therapeutic potential of botanicals: how medicinal plants targeting autophagy can reverse metabolic-associated fatty liver disease.Frontiers in pharmacology · 2026Review
- Article
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- Potential Role of Membrane Contact Sites in the Dysregulation of the Crosstalk Between Mitochondria and Lysosomes in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Blueprint of Collapse: Precision Biomarkers, Molecular Cascades, and the Engineered Decline of Fast-Progressing ALS.International journal of molecular sciences · 2025Review
- Review
- The many connections of UFMylation with Alzheimer's disease: a comprehensive review.Molecular neurodegeneration · 2025Review
- Enhanced differentiation of neural progenitor cells in Alzheimer's disease into vulnerable immature neurons.iScience · 2025Article
- Repurposing Sigma-1 Receptor-Targeting Drugs for Therapeutic Advances in Neurodegenerative Disorders.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The ER protein CANX (calnexin)-mediated autophagy protects against alzheimer disease.Autophagy · 2025Article
- Heavy metal-induced disruption of the autophagy-lysosomal pathway: implications for aging and neurodegenerative disorders.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Review
2 more citing papers are in PubMed but not listed here.
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13 authors at 4 institutions in 2 countries.
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Abstract
backgroundDysfunctional autophagy is implicated in Alzheimer's Disease (AD) pathogenesis. The alterations in the expression of many autophagy related genes (ATGs) have been reported in AD brains; however, the disparity of the changes confounds the role of autophagy in AD.
methodsTo further understand the autophagy alteration in AD brains, we analyzed transcriptomic (RNAseq) datasets of several brain regions (BA10, BA22, BA36 and BA44 in 223 patients compared to 59 healthy controls) and measured the expression of 130 ATGs. We used autophagy-deficient mouse models to assess the impact of the identified ATGs depletion on memory, autophagic activity and amyloid-β (Aβ) production.
resultsWe observed significant downregulation of multiple components of two autophagy kinase complexes BECN1-PIK3C3 and ULK1/2-FIP200 specifically in the parahippocampal gyrus (BA36). Most importantly, we demonstrated that deletion of NRBF2, a component of the BECN1-PIK3C3 complex, which also associates with ULK1/2-FIP200 complex, impairs memory in mice, alters long-term potentiation (LTP), reduces autophagy in mouse hippocampus, and promotes Aβ accumulation. Furthermore, AAV-mediated NRBF2 overexpression in the hippocampus not only rescues the impaired autophagy and memory deficits in NRBF2-depleted mice, but also reduces β-amyloid levels and improves memory in an AD mouse model.
conclusionsOur data not only implicates NRBF2 deficiency as a risk factor for cognitive impairment associated with AD, but also support the idea of NRBF2 as a potential therapeutic target for AD.
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