ArticleThe Journal of biological chemistry2008
Overexpression of neprilysin reduces alzheimer amyloid-beta42 (Abeta42)-induced neuron loss and intraneuronal Abeta42 deposits but causes a reduction in cAMP-responsive element-binding protein-mediated transcription, age-dependent axon pathology, and premature death in Drosophila.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 74 citations in OpenAlex.
- Targeting of neuroinflammation, oxidative stress, and synaptic dysfunction by vinpocetine in alzheimer's disease: a comprehensive appraisal.Metabolic brain disease · 2026Review
- Neprilysin-Mediated Amyloid Beta Clearance and Its Therapeutic Implications in Neurodegenerative Disorders.ACS pharmacology & translational science · 2024Review
- Comprehensive review on neprilysin (NEP) inhibitors: design, structure-activity relationships, and clinical applications.Frontiers in pharmacology · 2024Review
- Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective.Journal of cellular and molecular medicine · 2024Review
- Early Aβ42 Exposure Causes Learning Impairment in Later Life.Aging and disease · 2022Article
- Physiological clearance of amyloid-beta by the kidney and its therapeutic potential for Alzheimer's disease.Molecular psychiatry · 2021Article
- Identification and bioinformatic analysis of neprilysin and neprilysin-like metalloendopeptidases inmicroPublication biology · 2021Article
- Genetic Dissection of Alzheimer's Disease UsingInternational journal of molecular sciences · 2020Review
- Bridging the Gap Between Fluid Biomarkers for Alzheimer's Disease, Model Systems, and Patients.Frontiers in aging neuroscience · 2020Review
- Downregulation of RBO-PI4KIIIα Facilitates AβThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Phenotypic differences betweenAnimal cells and systems · 2017Article
- Modeling the complex pathology of Alzheimer's disease in Drosophila.Experimental neurology · 2015Review
- Differentially expressed genes linked to natural variation in long-term memory formation in Cotesia parasitic wasps.Frontiers in behavioral neuroscience · 2015Article
- A neuroprotective brain-penetrating endopeptidase fusion protein ameliorates Alzheimer disease pathology and restores neurogenesis.The Journal of biological chemistry · 2014Article
- Amyloid peptides ABri and ADan show differential neurotoxicity in transgenic Drosophila models of familial British and Danish dementia.Molecular neurodegeneration · 2014Article
- Amyloid-clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer's disease.Frontiers in aging neuroscience · 2014Review
- Intracellular cleavage of amyloid β by a viral protease NIa prevents amyloid β-mediated cytotoxicity.PloS one · 2014Article
- Neprilysin and Aβ Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer's Disease.Frontiers in aging neuroscience · 2013Review
- Integration of taste and calorie sensing in Drosophila.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Advances in the pathogenesis of Alzheimer's disease: a re-evaluation of amyloid cascade hypothesis.Translational neurodegeneration · 2012Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The amyloid-beta42 (Abeta42) peptide has been suggested to play a causative role in Alzheimer disease (AD). Neprilysin (NEP) is one of the rate-limiting Abeta-degrading enzymes, and its enhancement ameliorates extracellular amyloid pathology, synaptic dysfunction, and memory defects in mouse models of Abeta amyloidosis. In addition to the extracellular Abeta, intraneuronal Abeta42 may contribute to AD pathogenesis. However, the protective effects of neuronal NEP expression on intraneuronal Abeta42 accumulation and neurodegeneration remain elusive. In contrast, sustained NEP activation may be detrimental because NEP can degrade many physiological peptides, but its consequences in the brain are not fully understood. Using transgenic Drosophila expressing human NEP and Abeta42, we demonstrated that NEP efficiently suppressed the formation of intraneuronal Abeta42 deposits and Abeta42-induced neuron loss. However, neuronal NEP overexpression reduced cAMP-responsive element-binding protein-mediated transcription, caused age-dependent axon degeneration, and shortened the life span of the flies. Interestingly, the mRNA levels of endogenous fly NEP genes and phosphoramidon-sensitive NEP activity declined during aging in fly brains, as observed in mammals. Taken together, these data suggest both the protective and detrimental effects of chronically high NEP activity in the brain. Down-regulation of NEP activity in aging brains may be an evolutionarily conserved phenomenon, which could predispose humans to developing late-onset AD.
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