Association of <i>IGF1</i> gene polymorphism with Parkinson's disease in a Han Chinese population

Xiao, Yang; Cen, Luan; Mo, Mingshu; Chen, Xiang; Huang, Shuxuan; Wei, Lei; Li, Shaomin; Yang, Xinling; Qu, Shaogang; Pei, Zhong; Xu, Pingyi

doi:10.1002/jgm.2949

Cited by 6 publications

(7 citation statements)

References 46 publications

(55 reference statements)

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“…Moreover, the pharmaceutical role of IGF-1 has been confirmed in other animal models of neurodegeneration, such as multiple sclerosis (Akcali et al, 2017), Alzheimer’s (Zheng and Tong, 2017) and Parkinson’s disease (Xiao et al, 2017), which have a common neuropathology in excitotoxicity. Most interestingly, IGF-1 has been tested both in preclinical (Yao et al, 2008) and in open-label clinical trials for the treatment of cerebellar ataxia with encouraging results (Sanz-Gallego et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Astrocytic Insulin-Like Growth Factor-1 Protects Neurons Against Excitotoxicity

Chen

Tong

et al. 2019

Front. Cell. Neurosci.

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Background Exogenous insulin like growth factor-1 (IGF-1) is known to be neuroprotective in animal models with brain insults, while it can also cause hyperexcitability in rodents. In this regard, the role of endogenous IGF-1 in brain responses to brain insults like excitotoxicity, a common pathology in brain injuries, remains to be elucidated. Here, we investigated the potential role of cell-specific endogenous IGF-1 in the kainic acid (KA) -induced degeneration of the neurons. Methods Kainic acid was given to primary cultured cortical neurons and co-cultured astrocytes were added as a supportive system. We evaluated the cell proliferation rate, IGF-1 level in different groups and applied the PCR-Chip assay to explore the downstream of IGF-1. In addition, we applied the viral transfer of astrocytic IGF-1 to rodents treated with KA and assessed the associated molecular marker and behavioral outcomes in these rodents. Results We found KA induced increased cell death and hyperphosphorylated tau in neurons; co-cultured astrocytes could prevent these pathologies, and this rescuing effect was abrogated with blockade of the astrocytic IGF-1 with AG1024 (IGF-1R inhibitor). PCR-Chip assay identified that astrocytic IGF-1 could decrease the p-GSK-3 at Tyr 216 in neurons treated with KA and this effect was abrogated with AG1024 as well. In addition, in vivo study showed that gene transfer of astrocytic IGF-1 decreased p-tau and cognitive dysfunction in KA mice. Conclusion Our results show astrocytic IGF-1 exhibits neuroprotective properties in neurodegenerative processes in the CNS.

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Section: Introductionmentioning

confidence: 99%

Astrocytic Insulin-Like Growth Factor-1 Protects Neurons Against Excitotoxicity

Chen

Tong

et al. 2019

Front. Cell. Neurosci.

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“…237 Nevertheless it is clear that confounding factors, such as age and obesity limit the use of IGF-I as a predictive marker. 238 Association of an IGF-I gene polymorphism with PD has been demonstrated in a Chinese population 239 and is the same polymorphism as that associated with AD in the same population. 198 In postmortem brain tissue, IGF-I expression is increased in frontal cortex in PD compared to controls, while insulin, IGF-II, IR, IGF1R and IGF2R are reduced in white matter and amygdala.…”

Section: Neurodegenerative Disordersmentioning

confidence: 85%

The Role of Insulin-Like Growth Factors and Insulin-Like Growth Factor–Binding Proteins in the Nervous System

2019

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The insulin-like growth factors (IGF-I and IGF-II) and their receptors are widely expressed in nervous tissue from early embryonic life. They also cross the blood brain barriers by active transport, and their regulation as endocrine factors therefore differs from other tissues. In brain, IGFs have paracrine and autocrine actions that are modulated by IGF-binding proteins and interact with other growth factor signalling pathways. The IGF system has roles in nervous system development and maintenance. There is substantial evidence for a specific role for this system in some neurodegenerative diseases, and neuroprotective actions make this system an attractive target for new therapeutic approaches. In developing new therapies, interaction with IGF-binding proteins and other growth factor signalling pathways should be considered. This evidence is reviewed, gaps in knowledge are highlighted, and recommendations are made for future research.

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“…Blood samples were collected from all participants and genomic DNA was extracted from peripheral blood leukocytes using a Blood DNA Kit (Tiangen Biotech, Beijing, China) in accordance with the manufacturer's instructions . The genotypes of the three SNPs of interest were determined using the SNaPshot method of The Beijing Genomics Institute (Beijing, China) …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease (AD), globally affecting approximately 1% of individuals over 60 years of age and 4-5% of individuals over 85 years of age. [1][2][3] The neuropathological features of PD include a progressive loss of dopaminergic neurons in the substantia nigra and an aggregation of α-synuclein positive Lewy bodies in the surviving neurons. 4 PD is clinically characterized by progressive motor symptoms, including resting tremors, rigidity, bradykinesia and gait disturbances, as well as other non-motor symptoms, such as depression, autonomic dysfunction, sleep disorders, cognitive impairment and sensory abnormalities.…”

Section: Introductionmentioning

confidence: 99%

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