ArticleThe Journal of biological chemistry2014
A neuroprotective brain-penetrating endopeptidase fusion protein ameliorates Alzheimer disease pathology and restores neurogenesis.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Effects of 12 WeeksNutrients · 2021Trial
- Nanotechnology for efficient delivery of TCM active ingredients in treating brain diseases.Materials today. Bio · 2026Review
- Advanced Drug Delivery Strategies for Overcoming Biological Barriers: Tumor Microenvironment and Blood-Brain Barrier.Drugs in R&D · 2026Review
- A comprehensive review of the literature on CD10: its function, clinical application, and prospects.Frontiers in pharmacology · 2024Review
- Review
- A Historical Review of Brain Drug Delivery.Pharmaceutics · 2022Review
- Novel Brain-Penetrating Single Chain Antibodies Directed Against 3RTau for the Treatment of Alzheimer's Disease and Related Dementias.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Strategies for delivering therapeutics across the blood-brain barrier.Nature reviews. Drug discovery · 2021Review
- Bispecific Antibody Fragment Targeting APP and Inducing α-Site Cleavage Restores Neuronal Health in an Alzheimer's Mouse Model.Molecular neurobiology · 2019Article
- Systemic peptide mediated delivery of an siRNA targeting α-syn in the CNS ameliorates the neurodegenerative process in a transgenic model of Lewy body disease.Neurobiology of disease · 2019Article
- Selective targeting of 3 repeat Tau with brain penetrating single chain antibodies for the treatment of neurodegenerative disorders.Acta neuropathologica · 2018Article
- Brain-targeted stem cell gene therapy corrects mucopolysaccharidosis type II via multiple mechanisms.EMBO molecular medicine · 2018Article
- Extracellular Vesicles Secreted by Astroglial Cells Transport Apolipoprotein D to Neurons and Mediate Neuronal Survival Upon Oxidative Stress.Frontiers in cellular neuroscience · 2018Article
- Review
- New Insights into Epigenetic and Pharmacological Regulation of Amyloid-Degrading Enzymes.Neurochemical research · 2016Article
- Systemic Central Nervous System (CNS)-targeted Delivery of Neuropeptide Y (NPY) Reduces Neurodegeneration and Increases Neural Precursor Cell Proliferation in a Mouse Model of Alzheimer Disease.The Journal of biological chemistry · 2016Article
- A brain-targeted, modified neurosin (kallikrein-6) reduces α-synuclein accumulation in a mouse model of multiple system atrophy.Molecular neurodegeneration · 2015Article
- Applications of ApoB LDLR-Binding Domain Approach for the Development of CNS-Penetrating Peptides for Alzheimer's Disease.Methods in molecular biology (Clifton, N.J.) · 2015Article
- ESCRT-mediated uptake and degradation of brain-targeted α-synuclein single chain antibody attenuates neuronal degeneration in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Amyloid-clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer's disease.Frontiers in aging neuroscience · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer disease (AD) is characterized by widespread neurodegeneration throughout the association cortex and limbic system, deposition of amyloid-β peptide (Aβ) in the neuropil and around the blood vessels, and formation of neurofibrillary tangles. The endopeptidase neprilysin has been successfully used to reduce the accumulation of Aβ following intracranial viral vector delivery or ex vivo manipulated intracranial delivery. These therapies have relied on direct injections into the brain, whereas a clinically desirable therapy would involve i.v. infusion of a recombinant enzyme. We previously characterized a recombinant neprilysin that contained a 38-amino acid brain-targeting domain. Recombinant cell lines have been generated expressing this brain-targeted enzyme (ASN12). In this report, we characterize the ASN12 recombinant protein for pharmacology in a mouse as well as efficacy in two APPtg mouse models of AD. The recombinant ASN12 transited to the brain with a t½ of 24 h and accumulated to 1.7% of injected dose at 24 h following i.v. delivery. We examined pharmacodynamics in the tg2576 APPtg mouse with the prion promoter APP695 SWE mutation and in the Line41 mThy1 APP751 mutation mouse. Treatment of either APPtg mouse resulted in reduced Aβ, increased neuronal synapses, and improved learning and memory. In addition, the Line41 APPtg mice showed increased levels of C-terminal neuropeptide Y fragments and increased neurogenesis. These results suggest that the recombinant brain-targeted neprilysin, ASN12, may be an effective treatment for AD and warrant further investigation in clinical trials.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.