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Complement Componen...
Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis
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- Aeinehband, Shahin (author)
- Karolinska Institutet
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- Lindblom, Rickard P F (author)
- Uppsala universitet,Thoraxkirurgi,Karolinska Institutet
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- Al Nimer, Faiez (author)
- Karolinska Institutet
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- Vijayaraghavan, Swetha (author)
- Karolinska Institutet
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- Sandholm, Kerstin (author)
- Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Linnaeus Ctr Biomat Chem, BMC
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- Khademi, Mohsen (author)
- Karolinska Institutet
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- Olsson, Tomas (author)
- Karolinska Institutet
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- Nilsson, Bo (author)
- Uppsala universitet,Klinisk immunologi,Uppsala University
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- Nilsson Ekdahl, Kristina (author)
- Uppsala universitet,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Uppsala University,Linnaeus Ctr Biomat Chem, BMC,Klinisk immunologi
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- Darreh-Shori, Taher (author)
- Karolinska Institutet
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- Piehl, Fredrik (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2015-04-02
- 2015
- English.
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
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Abstract
Subject headings
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- Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genomewide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL), a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE) and BuChE, in cerebrospinal fluid (CSF) from patients with MS (n = 48) and non-inflammatory controls (n = 18). C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with >= 9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Annan medicin och hälsovetenskap -- Övrig annan medicin och hälsovetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Other Medical and Health Sciences -- Other Medical and Health Sciences not elsewhere specified (hsv//eng)
Keyword
- Immunologi
- Immunology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Aeinehband, Shah ...
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Lindblom, Rickar ...
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Al Nimer, Faiez
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Vijayaraghavan, ...
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Sandholm, Kersti ...
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Khademi, Mohsen
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show more...
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Olsson, Tomas
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Nilsson, Bo
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Nilsson Ekdahl, ...
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Darreh-Shori, Ta ...
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Piehl, Fredrik
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- MEDICAL AND HEALTH SCIENCES
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and Basic Medicine
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and Neurosciences
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Immunology
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and Other Medical an ...
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PLOS ONE
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Linnaeus University
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Uppsala University
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Karolinska Institutet