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Filtered Cerebrospinal Fluid From Patients With Amyotrophic Lateral Sclerosis Displays an Altered Proteome and Affects Motor Phenotype in a Mouse Model.

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العنوان: Filtered Cerebrospinal Fluid From Patients With Amyotrophic Lateral Sclerosis Displays an Altered Proteome and Affects Motor Phenotype in a Mouse Model.
المؤلفون: Venkatraman V; Department of Neurosurgery, Duke University Medical Center, Durham, USA., Filiano AJ; Department of Neurosurgery, Duke University Medical Center, Durham, USA., Xu L; Department of Neurosurgery, Duke University Medical Center, Durham, USA., Collins L; Molecular Education, Technology and Research Innovation Center (METRIC), North Carolina State University, Raleigh, USA., Luo E; Department of Neurosurgery, Duke University Medical Center, Durham, USA., Ripple KM; Department of Neurosurgery, Duke University Medical Center, Durham, USA., de Castro GC; Department of Neurosurgery, Duke University Medical Center, Durham, USA., Boua JK; Department of Neurosurgery, Duke University Medical Center, Durham, USA., Marius C; Department of Neurosurgery, Duke University Medical Center, Durham, USA., Giamberardino C; Department of Neurosurgery, Duke University Medical Center, Durham, USA., Lad SP; Department of Neurosurgery, Duke University Medical Center, Durham, USA., Islam Williams T; Molecular Education, Technology and Research Innovation Center (METRIC), North Carolina State University, Raleigh, USA., Bereman MS; Department of Biological Sciences, North Carolina State University, Raleigh, USA., Bedlack RS; Department of Neurology, Duke University Medical Center, Durham, USA.
المصدر: Cureus [Cureus] 2022 Dec 26; Vol. 14 (12), pp. e32980. Date of Electronic Publication: 2022 Dec 26 (Print Publication: 2022).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cureus, Inc Country of Publication: United States NLM ID: 101596737 Publication Model: eCollection Cited Medium: Print ISSN: 2168-8184 (Print) Linking ISSN: 21688184 NLM ISO Abbreviation: Cureus Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Palo Alto, CA : Cureus, Inc.
مستخلص: Introduction: Cerebrospinal fluid (CSF) has been implicated in amyotrophic lateral sclerosis (ALS) due to its ability to spread inflammatory proteins throughout the nervous system. We hypothesized that filtration of the CSF could remove pathogenic proteins and prevent them from altering motor phenotypes in a mouse model.
Methods: We filtered the CSF from 11 ALS patients via 100 kilodaltons (kD) molecular weight cut-off filters. We used mass spectrometry-based discovery proteomics workflows to compare protein abundances before and after filtration. To test the effects of CSF filtration on motor function, we injected groups of mice with saline, filtered ALS-CSF, or unfiltered ALS-CSF (n=12 per group) and assessed motor function via pole descent and open field tests.
Results: We identified proteins implicated in ALS pathogenesis and showed that these were removed in significant amounts in our workflow. Key filtered proteins included complement proteins, chitinases, serine protease inhibitors, and neuro-inflammatory proteins such as amyloid precursor protein, chromogranin A, and glial fibrillary acidic protein. Compared to the filtered ALS-CSF mice, unfiltered ALS-CSF mice took longer to descend a pole (10 days post-injection, 11.14 seconds vs 14.25 seconds, p = 0.02) and explored less on an open field (one day post-injection, 21.81 m vs 16.83 m, p = 0.0004).
Conclusions: We demonstrated the ability to filter proteins from the CSF of ALS patients and identified potentially pathologic proteins that were reduced in quantity. Additionally, we demonstrated the ability of unfiltered ALS-CSF to induce motor deficits in mice on the pole descent and open field tests and showed that filtration could prevent this deficit. Given the lack of effective treatments for ALS, this could be a novel solution for patients suffering from this deadly and irreversible condition.
Competing Interests: The authors have declared financial relationships, which are detailed in the next section.
(Copyright © 2022, Venkatraman et al.)
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فهرسة مساهمة: Keywords: amyotrophic lateral sclerosis; csf filtration; csf proteomics; mouse model; neurapheresis
تواريخ الأحداث: Date Created: 20230130 Latest Revision: 20230202
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9877488
DOI: 10.7759/cureus.32980
PMID: 36712738
قاعدة البيانات: MEDLINE
الوصف
تدمد:2168-8184
DOI:10.7759/cureus.32980