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The role of pro-inf...
The role of pro-inflammatory S100A9 in Alzheimer's disease amyloid-neuroinflammatory cascade
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- Wang, Chao (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Klechikov, Alexey G. (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Gharibyan, Anna L. (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Wärmländer, Sebastian K. T. S. (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- Jarvet, Jüri (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,National Institute of Chemical Physics & Biophysics (NICPB), Estonia
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Zhao, Lina (author)
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- Jia, Xueen (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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Shankar, S. K. (author)
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- Olofsson, Anders (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Brännström, Thomas (author)
- Umeå universitet,Patologi
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Mu, Yuguang (author)
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- Gräslund, Astrid (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- Morozova-Roche, Ludmilla A. (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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(creator_code:org_t)
- 2013-11-16
- 2014
- English.
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In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 127:4, s. 507-522
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Abstract
Subject headings
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- Pro-inflammatory S100A9 protein is increasingly recognized as an important contributor to inflammation-related neurodegeneration. Here, we provide insights into S100A9 specific mechanisms of action in Alzheimer's disease (AD). Due to its inherent amyloidogenicity S100A9 contributes to amyloid plaque formation together with A beta. In traumatic brain injury (TBI) S100A9 itself rapidly forms amyloid plaques, which were reactive with oligomer-specific antibodies, but not with A beta and amyloid fibrillar antibodies. They may serve as precursor-plaques for AD, implicating TBI as an AD risk factor. S100A9 was observed in some hippocampal and cortical neurons in TBI, AD and non-demented aging. In vitro S100A9 forms neurotoxic linear and annular amyloids resembling A beta protofilaments. S100A9 amyloid cytotoxicity and native S100A9 pro-inflammatory signaling can be mitigated by its co-aggregation with A beta, which results in a variety of micron-scale amyloid complexes. NMR and molecular docking demonstrated transient interactions between native S100A9 and A beta. Thus, abundantly present in AD brain pro-inflammatory S100A9, possessing also intrinsic amyloidogenic properties and ability to modulate A beta aggregation, can serve as a link between the AD amyloid and neuroinflammatory cascades and as a prospective therapeutic target.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- A beta
- Alzheimer's disease
- Amyloid
- Cytotoxicity
- Neuroinflammation
- S100A9
- Traumatic brain injury
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Wang, Chao
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Klechikov, Alexe ...
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Gharibyan, Anna ...
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Wärmländer, Seba ...
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Jarvet, Jüri
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Zhao, Lina
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show more...
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Jia, Xueen
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Shankar, S. K.
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Olofsson, Anders
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Brännström, Thom ...
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Mu, Yuguang
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Gräslund, Astrid
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Morozova-Roche, ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
- Articles in the publication
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Acta Neuropathol ...
- By the university
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Stockholm University
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Umeå University