Journal Article

Insulin‐Like Growth Factor Binding Protein 2 Drives Neurodegeneration in Parkinson's Disease: Insights From In Vivo and In Vitro Studies

Yu, Haiyang, Bu, Zhongqi, Wen, Lulu, An, Jing, Feng, Juan

2024

Overview

Aims Insulin‐like growth factor binding protein 2 (IGFBP2) is implicated in various neurodegenerative diseases. However, its role in Parkinson's disease (PD) is unclear. Methods PD rat model was established by 6‐OHDA injection. After 3 weeks, mRNA‐seq was conducted. Rats received rIGFBP2 via intra‐MFB injection 6 h prior to 6‐OHDA infusion, and the effect of IGFBP2 in PD rats was investigated by western blotting, IHC, specific kits, JC‐1 staining, and TUNEL analysis. In vitro, PC12 cells were treated with 6‐OHDA, and CCK‐8, specific kits, Hoechst 33258 staining, Western blotting, and JC‐1 staining were performed to assess the IGFBP2's role. Results mRNA‐seq revealed DEGs in PD, with attention to downregulated IGFBP2. rIGFBP2 treatment aggravated neurobehavioral deficits, decreased TH expression, Ψm, ATP level and SOD, GSH‐Px activities but increased α‐synuclein, ROS, MDA, mitochondrial cytochrome c contents, cell apoptosis in 6‐OHDA‐lesioned rats, which might be mediated through inactivating IGF‐1R/AKT pathway. In 6‐OHDA‐treated PC12 cells, rIGFBP2 aggravated cell injury, demonstrated by decreased cell viability and increased apoptosis, oxidative stress, and mitochondrial dysfunction. Co‐treatment with rIGFBP2 and rIGF‐1 partially reversed the effect of rIGFBP2 on cell damage. Conclusion IGFBP2 exacerbates neurodegeneration in PD through increasing oxidative stress, mitochondrial dysfunction, and apoptosis via inhibiting IGF‐1R/AKT pathway. The study demonstrates that rIGFBP2 treatment exacerbates Parkinson's disease through increasing oxidative stress, mitochondrial dysfunction, and apoptosis via the IGF‐1/IGF‐1R signaling pathway.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Adenosine triphosphate / AKT protein / Animals / Apoptosis / Apoptosis - drug effects / Apoptosis - physiology / Cell injury / Cell viability / Cholecystokinin / Cytochrome c / Insulin / Insulin-Like Growth Factor Binding Protein 2 - metabolism / Insulin-like growth factor-binding protein 2 / Insulin-like growth factors / Male / Mitochondria / mitochondria dysfunction / Movement disorders / mRNA / Neurodegeneration / Neurodegenerative diseases / Original / Oxidative stress / Oxidative Stress - drug effects / Oxidative Stress - physiology / Oxidopamine - toxicity / Parkinson Disease - metabolism / Parkinson Disease - pathology / Parkinson's disease / Parkinsonian Disorders - chemically induced / Parkinsonian Disorders - metabolism / Parkinsonian Disorders - pathology / PC12 Cells / Pheochromocytoma cells / Rats / Rats, Wistar / Receptor, IGF Type 1 - metabolism / Synuclein / Western blotting