ArticleeNeuro
Evidence for an Additive Neurorestorative Effect of Simultaneously Administered CDNF and GDNF in Hemiparkinsonian Rats: Implications for Different Mechanism of Action.
Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 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
- Redefining Parkinson's Disease management: the synergistic role of neurotrophic factors and mitochondria.Cellular and molecular life sciences : CMLS · 2026Review
- Neurotrophins as Potential Gene Therapy Targets for Huntington's Disease.Current gene therapy · 2025Review
- Neurotrophic factors for Parkinson's disease: Current status, progress, and remaining questions. Conclusions from a 2023 workshop.Journal of Parkinson's disease · 2024Review
- CDNF Exerts Anxiolytic, Antidepressant-like, and Procognitive Effects and Modulates Serotonin Turnover and Neuroplasticity-Related Genes.International journal of molecular sciences · 2024Article
- Potential Therapeutic Approach using Aromatic l-amino Acid Decarboxylase and Glial-derived Neurotrophic Factor Therapy Targeting Putamen in Parkinson's Disease.Current gene therapy · 2024Review
- Modulating Stress Proteins in Response to Therapeutic Interventions for Parkinson's Disease.International journal of molecular sciences · 2023Review
- Navigating the Landscape of MANF Research: A Scientometric Journey with CiteSpace Analysis.Cellular and molecular neurobiology · 2023Review
- CDNF rescues motor neurons in models of amyotrophic lateral sclerosis by targeting endoplasmic reticulum stress.Brain : a journal of neurology · 2023Article
- Beneficial behavioral effects of chronic cerebral dopamine neurotrophic factor (CDNF) infusion in the N171-82Q transgenic model of Huntington's disease.Scientific reports · 2023Article
- 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
- Modulating Microglia/Macrophage Activation by CDNF Promotes Transplantation of Fetal Ventral Mesencephalic Graft Survival and Function in a Hemiparkinsonian Rat Model.Biomedicines · 2022Article
- Cerebral dopamine neurotrophic factor transfection in dopamine neurons using neurotensin-polyplex nanoparticles reverses 6-hydroxydopamine-induced nigrostriatal neurodegeneration.Neural regeneration research · 2022Article
- Current knowledge and challenges associated with targeted delivery of neurotrophic factors into the central nervous system: focus on available approaches.Cell & bioscience · 2021Review
- 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
- CDNF: An innovative actor in disease-modifying approaches for Parkinson's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Endoplasmic Reticulum Stress Regulators: New Drug Targets for Parkinson's Disease.Journal of Parkinson's disease · 2021Review
- Protection of dopamine neurons by CDNF and neurturin variant N4 against MPP+ in dissociated cultures from rat mesencephalon.PloS one · 2021Article
- Cerebral dopamine neurotrophic factor (CDNF) protects against quinolinic acid-induced toxicity in in vitro and in vivo models of Huntington's disease.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder associated with a progressive loss of dopaminergic (DAergic) neurons of the substantia nigra (SN) and the accumulation of intracellular inclusions containing α-synuclein. Current therapies do not stop the progression of the disease, and the efficacy of these treatments wanes over time. Neurotrophic factors (NTFs) are naturally occurring proteins promoting the survival and differentiation of neurons and the maintenance of neuronal contacts. CDNF (cerebral dopamine NTF) and GDNF (glial cell line-derived NTF) are able to protect DAergic neurons against toxin-induced degeneration in experimental models of PD. Here, we report an additive neurorestorative effect of coadministration of CDNF and GDNF in the unilateral 6-hydroxydopamine (6-OHDA) lesion model of PD in rats. NTFs were given into the striatum four weeks after unilateral intrastriatal injection of 6-OHDA (20 µg). Amphetamine-induced (2.5 mg/kg, i.p.) rotational behavior was measured every two weeks. Number of tyrosine hydroxylase (TH)-positive cells from SN pars compacta (SNpc) and density of TH-positive fibers in the striatum were analyzed at 12 weeks after lesion. CDNF and GDNF alone restored the DAergic function, and one specific dose combination had an additive effect: CDNF (2.5µg) and GDNF (1µg) coadministration led to a stronger trophic effect relative to either of the single treatments alone. The additive effect may indicate different mechanism of action for the NTFs. Indeed, both NTFs activated the survival promoting PI3 kinase (PI3K)-Akt signaling pathway, but only CDNF decreased the expression level of tested endoplasmatic reticulum (ER) stress markers ATF6, glucose-regulated protein 78 (GRP78), and phosphorylation of eukaryotic initiation factor 2α subunit (eIF2α).
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