ArticleFrontiers in cell and developmental biology2021
Elevated Levels of miR-144-3p Induce Cholinergic Degeneration by Impairing the Maturation of NGF in Alzheimer's Disease.
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 31 citations in OpenAlex.
- MiR-144 Regulates Cognitive Dysfunction via NLRP3 Inflammasome and FoxO1/AdipoR Pathway in T2DM Mice.Molecular neurobiology · 2026Article
- The role of MicroRNAs in Alzheimer's disease: from pathogenesis to therapeutic potential.Molecular biology reports · 2026Review
- Neuroanatomical and neurochemical atlas of the spiny mouse (Acomys cahirinus) spinal cord.Brain structure & function · 2025Article
- Cpeb1 remodels cell type-specific translational program to promote fear extinction.Science advances · 2025Article
- From neuromodulation to bone homeostasis: therapeutic targets of nerve growth factor in skeletal diseases.Frontiers in pharmacology · 2025Review
- Neurochemical atlas of the rabbit spinal cord.Brain structure & function · 2024Article
- Exercise Alleviates Fluoride-Induced Learning and Memory Impairment in Mice: Role of miR-206-3p and PREG.Biological trace element research · 2024Article
- Insights into the Role of microRNAs as Clinical Tools for Diagnosis, Prognosis, and as Therapeutic Targets in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Electroacupuncture regulates Rab5a-mediating NGF transduction to improve learning and memory ability in the early stage of AD mice.CNS neuroscience & therapeutics · 2024Article
- Exploring small non-coding RNAs as blood-based biomarkers to predict Alzheimer's disease.Cell & bioscience · 2024Article
- Inhibition of miR-144-3p/FOXO1 Attenuates Diabetic Keratopathy Via Modulating Autophagy and Apoptosis.Investigative ophthalmology & visual science · 2024Article
- Non-Coding RNAs in the Regulation of Hippocampal Neurogenesis and Potential Treatment Targets for Related Disorders.Biomolecules · 2022Review
- Identification of Peripheral Blood miRNA Biomarkers in First-Episode Drug-Free Schizophrenia Patients Using Bioinformatics Strategy.Molecular neurobiology · 2022Article
- Therapeutic potential of neurotrophic factors in Alzheimer's Disease.Molecular biology reports · 2022Review
- Integrated analysis of the chemical-material basis and molecular mechanisms for the classic herbal formula of Lily Bulb and Rehmannia Decoction in alleviating depression.Chinese medicine · 2021Article
- A Review of miRNAs as Biomarkers and Effect of Dietary Modulation in Obesity Associated Cognitive Decline and Neurodegenerative Disorders.Frontiers in molecular neuroscience · 2021Review
- Individual and Combined Associations of Glucose Metabolic Components With Cognitive Function Modified by Obesity.Frontiers in endocrinology · 2021Article
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10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholinergic degeneration is one of the key pathological hallmarks of Alzheimer's disease (AD), a condition that is characterized by synaptic disorders and memory impairments. Nerve growth factor (NGF) is secreted in brain regions that receive projections from the basal forebrain cholinergic neurons. The trophic effects of NGF rely on the appropriate maturation of NGF from its precursor, proNGF. The ratio of proNGF/NGF is known to be increased in patients with AD; however, the mechanisms that underlie this observation have yet to be elucidated. Here, we demonstrated that levels of miR-144-3p are increased in the hippocampi and the medial prefrontal cortex of an APP/PS1 mouse model of AD. These mice also exhibited cholinergic degeneration (including the loss of cholinergic fibers, the repression of choline acetyltransferase (ChAT) activity, the reduction of cholinergic neurons, and an increased number of dystrophic neurites) and synaptic/memory deficits. The elevated expression of miR-144-3p specifically targets the mRNA of tissue plasminogen activator (tPA) and reduces the expression of tPA, thus resulting in the abnormal maturation of NGF. The administration of miR-144-3p fully replicated the cholinergic degeneration and synaptic/memory deficits observed in the APP/PS1 mice. The injection of an antagomir of miR-144-3p into the hippocampi partially rescued cholinergic degeneration and synaptic/memory impairments by restoring the levels of tPA protein and by correcting the ratio of proNGF/NGF. Collectively, our research revealed potential mechanisms for the disturbance of NGF maturation and cholinergic degeneration in AD and identified a potential therapeutic target for AD.
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