Back to Search
Start Over
Prion-like spreading of pathological α-synuclein in brain.
- Source :
-
Brain : a journal of neurology [Brain] 2013 Apr; Vol. 136 (Pt 4), pp. 1128-38. Date of Electronic Publication: 2013 Mar 06. - Publication Year :
- 2013
-
Abstract
- 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.
- Subjects :
- Administration, Intranasal
Animals
Behavior, Animal physiology
Brain physiopathology
Disease Models, Animal
Female
Humans
Injections, Intraventricular
Lewy Body Disease metabolism
Lewy Body Disease pathology
Lewy Body Disease physiopathology
Mice
Mice, Inbred C57BL
Recombinant Proteins administration & dosage
Recombinant Proteins toxicity
Time Factors
alpha-Synuclein administration & dosage
alpha-Synuclein toxicity
Brain metabolism
Brain pathology
Prions metabolism
alpha-Synuclein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2156
- Volume :
- 136
- Issue :
- Pt 4
- Database :
- MEDLINE
- Journal :
- Brain : a journal of neurology
- Publication Type :
- Academic Journal
- Accession number :
- 23466394
- Full Text :
- https://doi.org/10.1093/brain/awt037