ArticleJournal of neurochemistry2018
Delivery of an anti-transthyretin Nanobody to the brain through intranasal administration reveals transthyretin expression and secretion by motor neurons.
Article in Journal of neurochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Targeting mGlyR with nanobodies for depression.Nature communications · 2026Article
- Targeting transthyretin by one Cas9 variant with superfidelity and broad compatibility.Science advances · 2026Article
- Transthyretin, a novel prognostic marker of POCD revealed by time-series RNA-sequencing analysis.Molecular psychiatry · 2025Article
- Article
- PCSK9 inhibitor effectively alleviated cognitive dysfunction in a type 2 diabetes mellitus rat model.PeerJ · 2024Article
- The role of the ATP-adenosine axis in ischemic stroke.Seminars in immunopathology · 2023Review
- AAV-mediated delivery of an anti-BACE1 VHH alleviates pathology in an Alzheimer's disease model.EMBO molecular medicine · 2022Article
- Bivalent single domain antibody constructs for effective neutralization of Venezuelan equine encephalitis.Scientific reports · 2022Article
- Applications of nanobodies in brain diseases.Frontiers in immunology · 2022Review
- Effective targeting of microglial P2X7 following intracerebroventricular delivery of nanobodies and nanobody-encoding AAVs.Frontiers in pharmacology · 2022Article
- Central Nervous System Delivery of Antibodies and Their Single-Domain Antibodies and Variable Fragment Derivatives with Focus on Intranasal Nose to Brain Administration.Antibodies (Basel, Switzerland) · 2021Review
- The role of transthyretin in cell biology: impact on human pathophysiology.Cellular and molecular life sciences : CMLS · 2021Review
- Nusinersen Modulates Proteomics Profiles of Cerebrospinal Fluid in Spinal Muscular Atrophy Type 1 Patients.International journal of molecular sciences · 2021Article
- Brain Delivery of Single-Domain Antibodies: A Focus on VHH and VNAR.Pharmaceutics · 2020Review
- Neuronal megalin mediates synaptic plasticity-a novel mechanism underlying intellectual disabilities in megalin gene pathologies.Brain communications · 2020Article
- Gender-specific effects of transthyretin on neural stem cell fate in the subventricular zone of the adult mouse.Scientific reports · 2019Article
- Brain-targeted intranasal delivery of dopamine with borneol and lactoferrin co-modified nanoparticles for treating Parkinson's disease.Drug delivery · 2019Article
- PET imaging of distinct brain uptake of a nanobody and similarly-sized PAMAM dendrimers after intra-arterial administration.European journal of nuclear medicine and molecular imaging · 2019Article
- Transthyretin expression in the postischemic brain.PloS one · 2019Article
- Neuroanatomical Quantitative Proteomics Reveals Common Pathogenic Biological Routes between Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD).International journal of molecular sciences · 2018Review
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transthyretin (TTR) is a transport protein of retinol and thyroxine in serum and CSF, which is mainly secreted by liver and choroid plexus, and in smaller amounts in other cells throughout the body. The exact role of TTR and its specific expression in Central Nervous System (CNS) remains understudied. We investigated TTR expression and metabolism in CNS, through the intranasal and intracerebroventricular delivery of a specific anti-TTR Nanobody to the brain, unveiling Nanobody pharmacokinetics to the CNS. In TTR deficient mice, we observed that anti-TTR Nanobody was successfully distributed throughout all brain areas, and also reaching the spinal cord. In wild-type mice, a similar distribution pattern was observed. However, in areas known to be rich in TTR, reduced levels of Nanobody were found, suggesting potential target-mediated effects. Indeed, in wild-type mice, the anti-TTR Nanobody was specifically internalized in a receptor-mediated process, by neuronal-like cells, which were identified as motor neurons. Whereas in KO TTR mice Nanobody was internalized by all cells, for late lysosomal degradation. Moreover, we demonstrate that in vivo motor neurons also actively synthesize TTR. Finally, in vitro cultured primary motor neurons were also found to synthesize and secrete TTR into culture media. Thus, through a novel intranasal CNS distribution study with an anti-TTR Nanobody, we disclose a new cell type capable of synthesizing TTR, which might be important for the understanding of the physiological role of TTR, as well as in pathological conditions where TTR levels are altered in CSF, such as amyotrophic lateral sclerosis.
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