Wilson, Meghan E and Boumaza, Imene and Bowser, Robert
(2013)
Measurement of cystatin C functional activity in the cerebrospinal fluid of amyotrophic lateral sclerosis and control subjects.
Fluids Barriers CNS, 10 (1).
15 - ?.
ISSN 2045-8118
Abstract
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.
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Details
| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Wilson, Meghan E | | | | | Boumaza, Imene | | | | | Bowser, Robert | | | |
|
| Date: |
22 February 2013 |
| Date Type: |
Acceptance |
| Journal or Publication Title: |
Fluids Barriers CNS |
| Volume: |
10 |
| Number: |
1 |
| Page Range: |
15 - ? |
| DOI or Unique Handle: |
10.1186/2045-8118-10-15 |
| Schools and Programs: |
School of Medicine > Pathology |
| Refereed: |
Yes |
| ISSN: |
2045-8118 |
| Funders: |
NCATS NIH HHS (UL1 TR000005) |
| Date Deposited: |
07 Oct 2016 15:13 |
| Last Modified: |
20 Dec 2018 00:55 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/29744 |
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