Measurement of cystatin C functional activity in the cerebrospinal fluid of amyotrophic lateral sclerosis and control subjects
| Autor: | Meghan E. Wilson, Imene Boumaza, Robert Bowser |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
medicine.medical_specialty
Pathology Functional activity urologic and male genital diseases Neuroprotection Pathogenesis 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Cerebrospinal fluid Developmental Neuroscience Internal medicine medicine Cystatin C Amyotrophic lateral sclerosis reproductive and urinary physiology 030304 developmental biology 0303 health sciences Hematology biology business.industry Research General Medicine medicine.disease Cysteine protease female genital diseases and pregnancy complications 3. Good health Papain Endocrinology Neurology chemistry biology.protein business 030217 neurology & neurosurgery |
| Zdroj: | Fluids and Barriers of the CNS |
| ISSN: | 2045-8118 |
| DOI: | 10.1186/2045-8118-10-15 |
| Popis: | Background Cystatin C is a constitutively expressed and abundant cysteine protease inhibitor within the cerebrospinal fluid (CSF). Recent studies have reported a significant reduction in cystatin C concentration in the CSF of patients with amyotrophic lateral sclerosis (ALS) and several other neurodegenerative diseases, relative to healthy controls. Cystatin C can exhibit both neuroprotective and neurotoxic properties, suggesting that altered CSF cystatin C concentrations could potentially impact the pathogenesis or progression of these disorders. However, it is unclear if alterations in cystatin C concentration result in physiologically relevant differences in its functional activity within the CSF. Measurements of the cysteine protease inhibitory activity of cystatin C within the CSF have not been reported, and the relationship between CSF cystatin C concentration and activity levels in different disease contexts has not been investigated. Methods We used a papain inhibition assay to evaluate the total cystatin C activity in CSF samples from 23 ALS patients, 23 healthy controls, and 23 neurological disease controls. Cystatin C concentrations in these samples were previously measured by ELISA. Correlations between cystatin C concentration and activity were assessed with nonparametric statistics. Activity ratios were compared among diagnostic groups using both one-way ANOVA and repeated measures statistics. Results Total cystatin C activity was found to be directly proportional to its protein concentration in all subjects, and cystatin C activity was not altered in ALS patients. In addition, our data suggest that cystatin C is the predominant cysteine protease inhibitor in human CSF. Conclusions Our data demonstrate the successful measurement of the functional activity of cystatin C in the CSF, and show that total cystatin C activity can be inferred from its total protein concentration. Our results also suggest that cystatin C is the major cysteine protease inhibitor in human CSF and altered CSF cystatin C concentration may play a role in the pathobiology of ALS and other neurological diseases. |
| Databáze: | OpenAIRE |
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