Cystatin C Secretion in Blood Derivatives and Cellular Models of Idiopathic Parkinson's Disease.

IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY
Parkinson's Disease Pub Date : 2025-01-24 eCollection Date: 2025-01-01 DOI:10.1155/padi/5149071
Kathleen Mommaerts, Anna S Monzel, Alise Zagare, Sarah L Nickels, Nico J Diederich, Laura Longhino, William Mathieson, Paul M A Antony, Fay Betsou, Jens C Schwamborn
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引用次数: 0

Abstract

Parkinson's disease is an age-related progressive neurodegenerative disorder. A large majority of Parkinson's disease patients have an unknown etiology, which is classified as idiopathic Parkinson's disease. Generating disease models directly from idiopathic Parkinson's disease patients may improve the understanding of the disease pathology. Both neuroprotective and neurodegenerative roles have been suggested for cystatin C in neurodegenerative disease. In Parkinson's disease, investigations assessing cystatin C levels in different types of biospecimens such as blood, cerebrospinal fluid, and in vitro models have had conflicting results. We present a study assessing cystatin C levels in different biospecimen types originating from the same subjects. Using a sandwich ELISA, we compared cystatin C concentration in blood derivatives (plasma and serum) and culture media of derived models (stem cells, neuroepithelial stem cells, and midbrain organoids) of three idiopathic Parkinson's disease and three age-matched healthy control subjects with the same CST3 genotype. Genotyping analyses confirmed that all subjects were homozygous AA. The identity of the derived models was confirmed using immunohistochemical staining. Secreted cystatin C concentration was measured in each biospecimen tested. No statistically significant differences in cystatin C concentrations were found between the subjects in any of the biospecimen types. As a personalized marker, a higher cystatin C concentration was shown for some individual patients in the culture medium of midbrain organoids, suggesting a potential involvement in Parkinson's disease physiopathology. This proof of concept demonstrates that cystatin C is secreted by various idiopathic Parkinson's disease cell models, including midbrain organoids, which in turn suggests that cystatin C secretion by midbrain organoids might be pertinent in neurodegenerative disease research.

特发性帕金森病血液衍生物和细胞模型中胱抑素C的分泌
帕金森病是一种与年龄相关的进行性神经退行性疾病。绝大多数帕金森病患者病因不明,归类为特发性帕金森病。直接从特发性帕金森病患者中生成疾病模型可以提高对疾病病理的理解。胱抑素C在神经退行性疾病中具有神经保护和神经退行性作用。在帕金森病中,评估不同类型生物标本(如血液、脑脊液和体外模型)中胱抑素C水平的研究结果相互矛盾。我们提出了一项研究,评估来自同一受试者的不同生物标本类型的胱抑素C水平。采用夹心ELISA法,我们比较了3例特发性帕金森病患者和3例具有相同CST3基因型的健康对照者的衍生模型(干细胞、神经上皮干细胞和中脑类器官)的血液衍生物(血浆和血清)和培养基中的胱抑素C浓度。基因分型分析证实所有受试者均为纯合子AA。免疫组织化学染色证实了衍生模型的身份。测定每个被测生物标本中分泌的胱抑素C浓度。在任何生物标本类型的受试者之间,胱抑素C浓度没有统计学上的显著差异。作为一种个性化的标志物,在一些患者的中脑类器官培养基中显示出较高的胱抑素C浓度,提示其可能参与帕金森病的生理病理。这一概念证明,包括中脑类器官在内的多种特发性帕金森病细胞模型分泌胱抑素C,这表明中脑类器官分泌胱抑素C可能与神经退行性疾病的研究有关。
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来源期刊
Parkinson's Disease
Parkinson's Disease CLINICAL NEUROLOGY-
CiteScore
5.80
自引率
3.10%
发文量
0
审稿时长
18 weeks
期刊介绍: Parkinson’s Disease is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies related to the epidemiology, etiology, pathogenesis, genetics, cellular, molecular and neurophysiology, as well as the diagnosis and treatment of Parkinson’s disease.
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