Artikel
Neuroinvasion of α-synuclein prionoids after intraperitoneal injection
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Veröffentlicht: | 14. September 2016 |
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Gliederung
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Introduction: α-Synuclein is a soluble, cellular protein that in a number of neurodegenerative diseases forms pathologic protein deposits such as glial cytoplasmic inclusions in oligodendrocytes in multiple system atrophy or Lewy bodies in Parkinson’s disease. Misfolded α-synuclein has been reported to show a prion-like spread after intracerebral injection into transgenic and wild type mice.
Objectives: Here we investigated the potential of misfolded α-synuclein to induce disease after intraperitoneal challenge.
Materials & Methods: We used bigenic Tg (M83:Gfap-luc) mice that hemizygously express the A53T-mutant of human α-synuclein and firefly luciferase and when uninoculated remain healthy for over 600 d. These mice were injected with recombinant human wild type α-synuclein fibrils or phosphate-buffered saline as control into the peritoneal cavity.
Results: Intraperitoneal injection with α-synuclein fibrils but not phosphate-buffered saline led to neurologic disease with paralysis and kyphosis and α-synuclein pathology in the central nervous system of four out of five mice with a median incubation time of 229 ± 17 d. Diseased mice accumulated aggregates of sarkosyl-insoluble and phosphorylated α-synuclein in brain and spinal cord, which colocalized with ubiquitin and p62 and were accompanied by gliosis.
Conclusion: Our findings show that similar to prions, α-synuclein prionoids can neuroinvade the central nervous system after a single intraperitoneal injection and cause neuropathology and disease.