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Accumulation of alp...
Accumulation of alpha-synuclein within the liver, potential role in the clearance of brain pathology associated with Parkinsons disease
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- Reyes, Juan (författare)
- Linköpings universitet,Avdelningen för neurobiologi,Medicinska fakulteten,Linköping Univ, Dept Biomed & Clin Sci BKV, S-58185 Linköping, Sweden.;Linköping Univ, Dept Clin Pathol, S-58185 Linköping, Sweden.
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- Ekmark-Lewén, Sara (författare)
- Uppsala universitet,Geriatrik,Uppsala Univ, Sweden
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- Perdiki Grigoriadi, Marina (författare)
- Linköpings universitet,Avdelningen för neurobiologi,Medicinska fakulteten,Region Östergötland, Klinisk patologi,Linköping Univ, Dept Biomed & Clin Sci BKV, S-58185 Linköping, Sweden.;Linköping Univ, Dept Clin Pathol, S-58185 Linköping, Sweden.
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- Klingstedt, Therése (författare)
- Linköpings universitet,Kemi,Tekniska fakulteten,Linköping Univ, Dept Phys Chem & Biol, S-58183 Linköping, Sweden.
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- Hoffmann, Alana (författare)
- Friedrich Alexander Univ Erlangen Nurnberg, Dept Mol Neurol, Univ Hosp Erlangen, Erlangen, Germany.
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- Wiechec, Emilia (författare)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Linköping Univ, Dept Biomed & Clin Sci BKV, S-58185 Linköping, Sweden.;Linköping Univ, Dept Otorhinolaryngol, Anesthet Operat & Special Surg Ctr, S-58185 Linköping, Sweden.
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- Nilsson, Per (författare)
- Karolinska Institutet,Linköping Univ, Dept Phys Chem & Biol, S-58183 Linköping, Sweden.;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Div Neurogeriatr, S-17164 Solna, Sweden.
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- Nilsson, Peter, 1970- (författare)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Alafuzoff, Irina (författare)
- Uppsala universitet,Klinisk och experimentell patologi,Uppsala Univ Hosp, Sweden
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- Ingelsson, Martin (författare)
- Uppsala universitet,Geriatrik,Uppsala Univ, Sweden
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- Hallbeck, Martin (författare)
- Linköpings universitet,Avdelningen för neurobiologi,Medicinska fakulteten,Region Östergötland, Klinisk patologi,Linköping Univ, Dept Biomed & Clin Sci BKV, S-58185 Linköping, Sweden.;Linköping Univ, Dept Clin Pathol, S-58185 Linköping, Sweden.
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(creator_code:org_t)
- 2021-03-20
- 2021
- Engelska.
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Ingår i: Acta neuropathologica communications. - : BMC. - 2051-5960. ; 9:1
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https://liu.diva-por... (primary) (Raw object)
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https://actaneurocom...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Alpha-synuclein (alpha-syn) aggregation is the hallmark pathological lesion in brains of patients with Parkinsons disease (PD) and related neurological disorders characterized as synucleinopathies. Accumulating evidence now indicates that alpha-syn deposition is also present within the gut and other peripheral organs outside the central nervous system (CNS). In the current study, we demonstrate for the first time that alpha-syn pathology also accumulates within the liver, the main organ responsible for substance clearance and detoxification. We further demonstrate that cultured human hepatocytes readily internalize oligomeric alpha-syn assemblies mediated, at least in part, by the gap junction protein connexin-32 (Cx32). Moreover, we identified a time-dependent accumulation of alpha-syn within the liver of three different transgenic (tg) mouse models expressing human alpha-syn under CNS-specific promoters, despite the lack of alpha-syn mRNA expression within the liver. Such a brain-to-liver transmission route could be further corroborated by detection of alpha-syn pathology within the liver of wild type mice one month after a single striatal alpha-syn injection. In contrast to the synucleinopathy models, aged mice modeling AD rarely show any amyloid-beta (Ass) deposition within the liver. In human post-mortem liver tissue, we identified cases with neuropathologically confirmed alpha-syn pathology containing alpha-syn within hepatocellular structures to a higher degree (75%) than control subjects without alpha-syn accumulation in the brain (57%). Our results reveal that alpha-syn accumulates within the liver and may be derived from the brain or other peripheral sources. Collectively, our findings indicate that the liver may play a role in the clearance and detoxification of pathological proteins in PD and related synucleinopathies.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
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Reyes, Juan
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Ekmark-Lewén, Sa ...
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Perdiki Grigoria ...
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Klingstedt, Ther ...
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Hoffmann, Alana
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Wiechec, Emilia
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Nilsson, Per
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Nilsson, Peter, ...
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Alafuzoff, Irina
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Ingelsson, Marti ...
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Hallbeck, Martin
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Neurologi
- Artiklar i publikationen
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Acta neuropathol ...
- Av lärosätet
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Linköpings universitet
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Karolinska Institutet
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Uppsala universitet