Prion-like spreading of pathological α-synuclein in brain

By Masami Masuda-Suzukake, T. Nonaka, M. Hosokawa, Takayuki Oikawa, T. Arai, H. Akiyama, D. Mann, M. Hasegawa. Brain : a journal of neurology, 2013

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α-Synuclein is the major component of filamentous inclusions that constitute the defining characteristic of neurodegenerative α-synucleinopathies. However, the molecular mechanisms underlying α-synuclein accumulation and spread are unclear. Here we show that intracerebral injections of sarkosyl-insoluble α-synuclein from brains of patients with dementia with Lewy bodies induced hyperphosphorylated α-synuclein pathology in wild-type mice. Furthermore, injection of fibrils of recombinant human and mouse α-synuclein efficiently induced similar α-synuclein pathologies in wild-type mice. C57BL/6J mice injected with α-synuclein fibrils developed abundant Lewy body/Lewy neurite-like pathology, whereas mice injected with soluble α-synuclein did not. Immunoblot analysis demonstrated that endogenous mouse α-synuclein started to accumulate 3 months after inoculation, while injected human α-synuclein fibrils disappeared in about a week. These results indicate that α-synuclein fibrils have prion-like properties and inoculation into wild-type brain induces α-synuclein pathology in vivo. This is a new mouse model of sporadic α-synucleinopathy and should be useful for elucidating progression mechanisms and evaluating disease-modifying therapy.

Subfields: Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/d0d04efb5aa2c293f7047b33a3c7e08a0413cfc0

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In Neurology

  1. M. Hasegawa
  2. M. Goedert

In Physiology

  1. M. Goedert
  2. T. Tomita

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