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Binding of alfa-syn...
Binding of alfa-synuclein oligomers to Cx32 facilitates protein uptake and transfer in neurons and oligodendrocytes
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- Reyes, Juan (author)
- Linköpings universitet,Avdelning för neurobiologi,Medicinska fakulteten
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- Sackmann, Christopher (author)
- Linköpings universitet,Avdelning för neurobiologi,Medicinska fakulteten
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- Hoffmann, Alana (author)
- Univ Hosp Erlangen, Dept Mol Neurol, Erlangen, Germany
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- Svenningsson, Per (author)
- Karolinska Institutet,Karolinska Inst, Sweden
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- Winkler, Jürgen (author)
- Univ Hosp Erlangen, Dept Mol Neurol, Erlangen, Germany
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- Ingelsson, Martin (author)
- Uppsala universitet,Geriatrik,Uppsala Univ, Sweden
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- Hallbeck, Martin (author)
- Linköpings universitet,Avdelning för neurobiologi,Medicinska fakulteten,Region Östergötland, Klinisk patologi
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(creator_code:org_t)
- 2019-04-11
- 2019
- English.
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In: Acta Neuropathologica. - : SPRINGER. - 0001-6322 .- 1432-0533. ; 138:1, s. 23-47
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Abstract
Subject headings
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- The intercellular transfer of alpha-synuclein (-syn) has been implicated in the progression of Parkinson's disease (PD) and multiple system atrophy (MSA). The cellular mechanisms underlying this process are now beginning to be elucidated. In this study, we demonstrate that the gap junction protein connexin-32 (Cx32) is centrally involved in the preferential uptake of -syn oligomeric assemblies (o-syn) in neurons and oligodendrocytes. In vitro, we demonstrate a clear correlation between Cx32 expression and o-syn uptake. Pharmacological and genetic strategies targeting Cx32 successfully blocked o-syn uptake. In cellular and transgenic mice modeling PD and MSA, we observed significant upregulation of Cx32 which correlates with -syn accumulation. Notably, we could alsodemonstrate a direct interaction between -syn and Cx32 in two out of four human PD cases that was absent in all four age-matched controls. These data are suggestive of a link between Cx32 and PD pathophysiology. Collectively, our results provide compelling evidence for Cx32 as a novel target for therapeutic intervention in PD and related -synucleinopathies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Parkinson's disease (PD)
- Multiple system atrophy (MSA)
- Alzheimer's disease (AD)
- Cell-to-cell transfer
- Prion-like transfer
- Gap junction proteins
- Cx32
- GJB1
- alpha-Synuclein (-syn)
Publication and Content Type
- ref (subject category)
- art (subject category)
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