ArticleCell transplantation2019
Characterization of CDNF-Secreting ARPE-19 Cell Clones for Encapsulated Cell Therapy.
Article in Cell transplantation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Neuroprotective and reparative effects of endoplasmic reticulum luminal proteins - mesencephalic astrocyte-derived neurotrophic factor and cerebral dopamine neurotrophic factor.Croatian medical journal · 2019Pooled it
- Delivery of CDNF by AAV-mediated gene transfer protects dopamine neurons and regulates ER stress and inflammation in an acute MPTP mouse model of Parkinson's disease.Scientific reports · 2024Article
- CDNF and MANF in the brain dopamine system and their potential as treatment for Parkinson's disease.Frontiers in psychiatry · 2023Review
- CDNF Interacts with ER Chaperones and Requires UPR Sensors to Promote Neuronal Survival.International journal of molecular sciences · 2022Article
- Human-Specific Regulation of Neurotrophic Factors MANF and CDNF by microRNAs.International journal of molecular sciences · 2021Article
- Cerebral dopamine neurotrophic factor reduces α-synuclein aggregation and propagation and alleviates behavioral alterations in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Neurotrophic factors for disease-modifying treatments of Parkinson's disease: gaps between basic science and clinical studies.Pharmacological reports : PR · 2020Review
- Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebral dopamine neurotrophic factor (CDNF) shows beneficial effects in rodent models of Parkinson's and Alzheimer's disease. The brain is a challenging target for protein therapy due to its exclusive blood-brain barrier. Hence, the therapeutic protein should be delivered directly to the brain parenchyma. Implantation of encapsulated mammalian cells that constantly secrete CDNF is a potential approach for targeted and long-term protein delivery to the brain. In this study, we generated several CDNF-secreting cell clones derived from human retinal pigment epithelial cell line ARPE-19, and studied CDNF secretion from the clones maintained as monolayers and in polymeric microcapsules. The secretion of wild type (wt) CDNF transgene was low and the majority of the produced protein remained intracellular, locating mainly to the endoplasmic reticulum (ER). The secretion of wtCDNF decreased to even lower levels when the clones were in a non-dividing state, as in the microcapsules. Both codon optimization and deletion of the putative ER-retrieval signal (four last amino acids: KTEL) improved CDNF secretion. More importantly, the secretion of KTEL-deleted CDNF remained constant in the non-dividing clones. Thus, cells expressing KTEL-deleted CDNF, in contrast to wtCDNF, can be considered for cell encapsulation applications if the KTEL-deleted CDNF is proven to be biologically active
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