ArticleNeural regeneration research2021
Glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide dual receptor agonist DA-CH5 is superior to exendin-4 in protecting neurons in the 6-hydroxydopamine rat Parkinson model.
Article in Neural regeneration research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.
- The effect of GLP-1 receptor agonists on autophagy: insights gathered from research evaluating neurodegenerative disorders with these agents.Acta neuropsychiatrica · 2026Pooled it
- Association of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and neurogenesis: a systematic review.Acta neuropsychiatrica · 2025Pooled it
- The role of the incretin GIP in inflammation.Journal of endocrinological investigation · 2026Review
- The novel GLP-1/GIP dual receptor agonist DA5-CH is superior to tirzepatide and exendin-4 in the 6-OHDA Parkinson rat model.Frontiers in endocrinology · 2026Article
- Review
- Novel GLP-1/GIP Dual Receptor Agonist Alleviates Neonatal Hypoxic-Ischemic Encephalopathy by Inhibiting TLR2/NF-κB/NLRP3 Mediated-Neuroinflammation : The role of DA5-CH in neonatal hypoxic-ischemic encephalopathy.Neurochemical research · 2025Article
- GABA and GLP-1 receptor agonist combination therapy modifies diabetes and Langerhans islet cytoarchitecture in a rat model of Wolfram syndrome.Diabetology & metabolic syndrome · 2025Article
- The role of amphipathic and cationic helical peptides in Parkinson's disease.Protein science : a publication of the Protein Society · 2025Review
- Activation of GLP-1R modulates the spontaneous discharge of nigral dopaminergic neurons and motor behavior in mice with chronic MPTP Parkinson's disease.Frontiers in aging neuroscience · 2025Article
- GLP-1 Receptor Agonists: A New Treatment in Parkinson's Disease.International journal of molecular sciences · 2024Review
- Anti-inflammatory role of glucagon-like peptide 1 receptor agonists and its clinical implications.Therapeutic advances in endocrinology and metabolism · 2024Review
- Exosomes derived from human umbilical cord mesenchymal stem cells alleviate Parkinson's disease and neuronal damage through inhibition of microglia.Neural regeneration research · 2023Article
- Exendin-4 and linagliptin attenuate neuroinflammation in a mouse model of Parkinson's disease.Neural regeneration research · 2023Article
- Treatment with the dual-incretin agonist DA-CH5 demonstrates potent therapeutic effect in a rat model of Wolfram Syndrome.Frontiers in endocrinology · 2023Article
- Alpha synuclein post translational modifications: potential targets for Parkinson's disease therapy?Frontiers in molecular neuroscience · 2023Review
- A Dual GLP-1/GIP Receptor Agonist Is More Effective than Liraglutide in the A53T Mouse Model of Parkinson's Disease.Parkinson's disease · 2023Article
- (D-Ser2) oxyntomodulin recovers hippocampal synaptic structure and theta rhythm in Alzheimer's disease transgenic mice.Neural regeneration research · 2022Article
- Anti-Inflammatory Effects of GLP-1 Receptor Activation in the Brain in Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Parkinson's Disease and Sugar Intake-Reasons for and Consequences of a Still Unclear Craving.Nutrients · 2022Review
- Parkinson's disease and diabetes mellitus: common mechanisms and treatment repurposing.Neural regeneration research · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with Parkinson's disease (PD) have impaired insulin signaling in the brain. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), can re-sensitize insulin signaling. In a recent phase II clinical trial, the first GLP-1 mimic, exendin-4, has shown reliable curative effect in patients with PD. DA-CH5 is a novel GLP-1/GIP receptor unimolecular co-agonist with a novel peptide sequence added to cross the blood-brain barrier. Here we showed that both exendin-4 and DA-CH5 protected against 6-hydroxydopamine (6-OHDA) cytotoxicity, inhibited apoptosis, improved mitogenesis and induced autophagy flux in SH-SY5Y cells via activation of the insulin receptor substrate-1 (IRS-1)/alpha serine/threonine-protein kinase (Akt)/cAMP response element-binding protein (CREB) pathway. We also found that DA-CH5 (10 nmol/kg) daily intraperitoneal administration for 30 days post-lesion alleviated motor dysfunction in rats and prevented stereotactic unilateral administration of 6-OHDA induced dopaminergic neurons loss in the substantia nigra pars compacta. However, DA-CH5 showed curative effects in reducing the levels of α-synuclein and the levels of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β). It was also more effective than exendin-4 in inhibiting apoptotic process and protecting mitochondrial functions. In addition, insulin resistance was largely alleviated and the expression of autophagy-related proteins was up-regulated in PD model rats after DA-CH5 treatment. These results in this study indicate DA-CH5 plays a therapeutic role in the 6-OHDA-unilaterally lesioned PD rat model and is superior to GLP-1 analogue exendin-4. The study was approved by the Animal Ethics Committee of Shanxi Medical University of China.
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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.