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Neuropeptide Y (NPY...
Neuropeptide Y (NPY) in cerebrospinal fluid from patients with Huntington's Disease : increased NPY levels and differential degradation of the NPY1-30 fragment
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- Wagner, Leona (författare)
- Deutschsprachige Selbsthilfegruppe für Alkaptonurie e.V
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- Björkqvist, Maria (författare)
- Lund University,Lunds universitet,Biomarkörer vid hjärnsjukdomar,Forskargrupper vid Lunds universitet,Translationell neuroendokrinologi,Biomarkers in Brain Disease,Lund University Research Groups,Translational Neuroendocrinology
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- Hult Lundh, Sofia (författare)
- Lund University,Lunds universitet,Translationell neuroendokrinologi,Forskargrupper vid Lunds universitet,Translational Neuroendocrinology,Lund University Research Groups
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- Wolf, Raik (författare)
- Klinikum St. Georg, Leipzig
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- Börgel, Arne (författare)
- Johannes-Gutenberg University Mainz
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- Schlenzig, Dagmar (författare)
- Probiodrug AG
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Ludwig, Hans-Henning (författare)
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- Rahfeld, Jens-Ulrich (författare)
- Probiodrug AG
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- Leavitt, Blair (författare)
- Johannes-Gutenberg University Mainz
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- Demuth, Hans-Ulrich (författare)
- Probiodrug AG
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- Petersén, Åsa (författare)
- Lund University,Lunds universitet,Biomarkörer vid hjärnsjukdomar,Forskargrupper vid Lunds universitet,Biomarkers in Brain Disease,Lund University Research Groups
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- von Hörsten, Stephan (författare)
- Fraunhofer Institute for Cell Therapy and Immunology
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Deutschsprachige Selbsthilfegruppe für Alkaptonurie eV Biomarkörer vid hjärnsjukdomar (creator_code:org_t)
- 2016-05-20
- 2016
- Engelska.
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Ingår i: Journal of Neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 137:5, s. 820-837
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Huntington's disease (HD) is an inherited and fatal polyglutamine neurodegenerative disorder caused by an expansion of the CAG triplet repeat coding region within the HD gene. Progressive dysfunction and loss of striatal GABAergic medium spiny neurons (MSNs) may account for some of the characteristic symptoms in HD patients. Interestingly, in HD, MSNs expressing neuropeptide Y (NPY) are spared and their numbers is even up-regulated in HD patients. In line with this, we report here on increased immuno-linked NPY (IL-NPY) levels in human cerebrospinal fluid (hCSF) from HD patients. As this antibody-based detection of NPY may provide false positive differences due to the antibody-based detections of only fragments of NPY, the initial finding was validated by investigating the proteolytic stability of NPY in hCSF using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and selective inhibitors. A comparison between resulting NPY-fragments and detailed epitope analysis verified significant differences of IL-NPY1-36/3-36 and NPY1-30 levels between HD patients and control subjects. Ex vivo degradomics analysis demonstrated that NPY is initially degraded to NPY1-30 by cathepsin D (CTSD) in both HD patients and control subjects. Yet, NPY1-30 is then further differentially hydrolyzed by thimet oligopeptidase (TOP) in HD patients and by neprilysin (NEP) in control subjects. Furthermore, altered hCSF TOP-inhibitor Dynorphin A1-13 (Dyn-A1-13 ) and TOP-substrate Dyn-A1-8 levels indicate an impaired Dyn-A-TOP network in HD patients. Thus, we conclude that elevated IL-NPY-levels in conjunction with TOP- / NEP-activity/protein as well as Dyn-A1-13 -protein levels may serve as a potential biomarker in human CSF of HD. This article is protected by copyright. All rights reserved.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Huntington′s disease
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Wagner, Leona
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Björkqvist, Mari ...
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Hult Lundh, Sofi ...
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Wolf, Raik
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Börgel, Arne
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Schlenzig, Dagma ...
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visa fler...
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Ludwig, Hans-Hen ...
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Rahfeld, Jens-Ul ...
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Leavitt, Blair
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Demuth, Hans-Ulr ...
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Petersén, Åsa
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von Hörsten, Ste ...
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