ArticlePloS one2020
Brain Shuttle Neprilysin reduces central Amyloid-β levels.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 60 citations in OpenAlex.
- Article
- Antibody-Based Biologics for CNS Disorders.Antibodies (Basel, Switzerland) · 2026Review
- Brain Delivery of Antibody-Derived Biologicals for Alzheimer's Disease: An Updated Narrative Review.Antibodies (Basel, Switzerland) · 2026Review
- Bispecific brain-penetrant antibodies for treatment of Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Review
- Advances in Neurodegenerative Disease Therapy: Stem Cell Clinical Trials and Promise of Engineered Exosomes.CNS neuroscience & therapeutics · 2025Review
- Drug delivery strategies to cross the blood-brain barrier in Alzheimer's disease: a comprehensive review on three promising strategies.The journal of prevention of Alzheimer's disease · 2025Review
- Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer's disease.medRxiv : the preprint server for health sciences · 2024Article
- Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer's disease mice.Journal of translational medicine · 2024Article
- Receptor-mediated transcytosis for brain delivery of therapeutics: receptor classes and criteria.Frontiers in drug delivery · 2024Review
- Fc-Engineered Therapeutic Antibodies: Recent Advances and Future Directions.Pharmaceutics · 2023Review
- CD98hc is a target for brain delivery of biotherapeutics.Nature communications · 2023Article
- ImmunoPET imaging of amyloid-beta in a rat model of Alzheimer's disease with a bispecific, brain-penetrating fusion protein.Translational neurodegeneration · 2022Article
- Blood-brain barrier penetrating neprilysin degrades monomeric amyloid-beta in a mouse model of Alzheimer's disease.Alzheimer's research & therapy · 2022Article
- ERp57 chaperon protein protects neuronal cells from Aβ-induced toxicity.Journal of neurochemistry · 2022Article
- All roads lead to Rome - a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer's disease.Neural regeneration research · 2022Review
- Insights of Extracellular Vesicles of Mesenchymal Stem Cells: a Prospective Cell-Free Regenerative Medicine for Neurodegenerative Disorders.Molecular neurobiology · 2022Review
- Amyloid Beta Dynamics in Biological Fluids-Therapeutic Impact.Journal of clinical medicine · 2021Review
- Redox-Active Metal Ions and Amyloid-Degrading Enzymes in Alzheimer's Disease.International journal of molecular sciences · 2021Review
- Enhanced neprilysin-mediated degradation of hippocampal Aβ42 with a somatostatin peptide that enters the brain.Theranostics · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reducing Amyloid β (Aβ) in the brain is of fundamental importance for advancing the therapeutics for Alzheimer`s disease. The endogenous metallopeptidase neprilysin (NEP) has been identified as one of the key Aβ-degrading enzymes. Delivery of NEP to the brain by utilizing the Brain Shuttle (BS) transport system offers a promising approach for clearing central Aβ. We fused the extracellular catalytic domain of NEP to an active or inactive BS module. The two BS-NEP constructs were used to investigate the pharmacokinetic/pharmacodynamics relationships in the blood and the cerebrospinal fluid (CSF) in dose-response and multiple dosing. As previously shown, NEP was highly effective at degrading Aβ in blood but not in the CSF compartment after systemic administration. In contrast, the NEP with an active BS module led to a significant CSF exposure of BS-NEP, followed by substantial Aβ reduction in CSF and brain parenchyma. Our data show that a BS module against the transferrin receptor facilitates the transport of an Aβ degrading enzyme across the blood-brain barriers to efficiently reduce Aβ levels in both CSF and brain.
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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.