DOPAL is transmissible to and oligomerizes alpha-synuclein in human glial cells

Autonomic Neuroscience : Basic & Clinical
Yunden JinsmaaDavid S Goldstein

Abstract

Glial cytoplasmic inclusions (GCIs) containing alpha-synuclein (AS) are a neuropathologic hallmark of multiple system atrophy (MSA). Oligomerized AS is thought to be the pathogenic form of the protein. Glial cells normally express little AS, but they can take up AS from the extracellular fluid. 3,4-Dihydroxyphenylacetaldehyde (DOPAL), an obligate intermediate in the intra-neuronal metabolism of dopamine (DA), potently oligomerizes AS. In this study we tested whether DOPAL is taken up by human glial cells and augments intracellular oligomerization of AS. DOPAL (exogenous or endogenous from co-incubation with PC12 cells) and AS (native or A53T mutant form) were added to the incubation medium of glial cells (glioblastoma or MO3.13 oligodendrocytes). Glial cellular contents of DOPAL and its intracellular metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were measured at up to 180 min of incubation. Glial cellular AS oligomers were quantified by Western blotting. Neither glioblastoma nor MO3.13 cells contained endogenous catecholamines or AS. Co-incubation of the cells with DA-producing PC12 cells produced time-related increases in DOPAL and DOPAC contents. Similarly, glial cellular DOPAL and DOPAC contents increased rapidly after a...Continue Reading

References

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Citations

Apr 28, 2018·The Journal of Pharmacology and Experimental Therapeutics·Yunden JinsmaaDavid S Goldstein
Sep 7, 2019·Molecular Neurodegeneration·Anna MasatoLuigi Bubacco
Dec 11, 2020·NPJ Parkinson's Disease·Meghan L BucherTeresa G Hastings
Jan 6, 2021·Communications Biology·Rodrigo CataldiMichele Vendruscolo

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