ArticleTranslational neurodegeneration2024
Agomirs upregulating carboxypeptidase E expression rescue hippocampal neurogenesis and memory deficits in Alzheimer's disease.
Article in Translational neurodegeneration, 2024. 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, 12 citations in OpenAlex.
- Molecular interplay between Non-coding RNAs and BDNF in Neurodegenerative Disorders: a systematic review.Molecular biology reports · 2026Pooled it
- BDNF-Hyaluronic Acid Hydrogel Promotes Neuronal Differentiation of Neural Stem Cells in Aβ-Induced Injury and 5×FAD Mice.Biomedicines · 2026Article
- The Mechanism of Carboxypeptidase E Regulating NLRP3 Inflammasome Signaling in the Pathogenesis of Depression-Like Behaviors in Mice.Neuroimmunomodulation · 2026Article
- Neurotrophic factor-α1/carboxypeptidase E regulates critical protein networks to rescue neurodegeneration, defective synaptogenesis and impaired autophagy in Alzheimer's disease mice.Translational neurodegeneration · 2025Article
- Predicted molecules followed by experimental validation for protecting human neurons from oxidative stress-induced cytotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A microsphere loaded with chondrocyte-targeting exosomes continuously deliver miR-148a for osteoarthritis therapy.Materials today. Bio · 2025Article
- Single-Cell RNA Sequencing of the Primary Visual Cortex in Mice With Optic Nerve Injury.Investigative ophthalmology & visual science · 2025Article
- Mendelian Randomization Estimates the Effects of Plasma and Cerebrospinal Fluid Proteins on Intelligence, Fluid Intelligence Score, and Cognitive Performance.Molecular neurobiology · 2025Article
- Exploring the role of Transcranial magnetic stimulation in cognitive impairment and sarcopenia: a narrative review.Frontiers in human neuroscience · 2025Review
- Neurotrophic factor alpha 1 gene therapy in Alzheimer's disease: scope and advancements.Frontiers in molecular neuroscience · 2025Review
- Neurotrophic factor-α1/carboxypeptidase E controls progression and reversal of Alzheimer's disease pathogenesis in mice.Theranostics · 2025Article
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Authors and funding
15 authors at 2 institutions in 3 countries.
Funding
Abstract
backgroundAdult neurogenesis occurs in the subventricular zone (SVZ) and the subgranular zone of the dentate gyrus in the hippocampus. The neuronal stem cells in these two neurogenic niches respond differently to various physiological and pathological stimuli. Recently, we have found that the decrement of carboxypeptidase E (CPE) with aging impairs the maturation of brain-derived neurotrophic factor (BDNF) and neurogenesis in the SVZ. However, it remains unknown whether these events occur in the hippocampus, and what the role of CPE is in the adult hippocampal neurogenesis in the context of Alzheimer's disease (AD).
methodsIn vivo screening was performed to search for miRNA mimics capable of upregulating CPE expression and promoting neurogenesis in both neurogenic niches. Among these, two agomirs were further assessed for their effects on hippocampal neurogenesis in the context of AD. We also explored whether these two agomirs could ameliorate behavioral symptoms and AD pathology in mice, using direct intracerebroventricular injection or by non-invasive intranasal instillation.
resultsRestoration of CPE expression in the hippocampus improved BDNF maturation and boosted adult hippocampal neurogenesis. By screening the miRNA mimics targeting the 5'UTR region of Cpe gene, we developed two agomirs that were capable of upregulating CPE expression. The two agomirs significantly rescued adult neurogenesis and cognition, showing multiple beneficial effects against the AD-associated pathologies in APP/PS1 mice. Of note, noninvasive approach via intranasal delivery of these agomirs improved the behavioral and neurocognitive functions of APP/PS1 mice.
conclusionsCPE may regulate adult hippocampal neurogenesis via the CPE-BDNF-TrkB signaling pathway. This study supports the prospect of developing miRNA agomirs targeting CPE as biopharmaceuticals to counteract aging- and disease-related neurological decline in human brains.
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