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A novel animal mode...
A novel animal model for Parkinson's disease based on in vivo effects of small-molecule of alpha-synuclein
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- Chermenina, Maria, 1978- (författare)
- Umeå universitet,Histologi med cellbiologi
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- Chorell, Erik, 1980- (författare)
- Umeå universitet,Kemiska institutionen,Fredrik Almqvist
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- Henrik, Antti (författare)
- Umeå universitet,Kemiska institutionen
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visa fler...
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- Almqvist, Fredrik, 1967- (författare)
- Umeå universitet,Kemiska institutionen
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- Wittung-Stafshede, Pernilla (författare)
- Umeå universitet,Kemiska institutionen
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- Strömberg, Ingrid (författare)
- Umeå universitet,Histologi med cellbiologi
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visa färre...
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(creator_code:org_t)
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- Amyloid fibrils of alpha-synuclein are major constituents of Lewy bodies, the pathological hallmark of Parkinson’s disease. Monomeric α-synuclein is involved in synaptic vesicle trafficking and long-term maintenance of neurons. The underlying mechanisms of Parkinson’s disease are not known but it has been proposed that oligomers of α-synuclein, formed during the aggregation process, are toxic to neurons. To search for a new animal model of Parkinson’s disease, here we capitalized on the in vitro discovery of a small-molecule templator of α-synuclein fibrillization, the 2-pyridone, FN075. FN075 and MS382, another 2-pyridone variant that act as an inhibitor of amyloids in vitro, were injected into the striatum or substantia nigra of normal C57Bl/6 mice. No acute toxicity of the compounds was detected, as there was 100 % survival of the injected mice. At 6 months after the striatal injection, sensorimotor functions were impaired with no reduction in TH-positive neurons in the substantia nigra in mice injected with FN075, whereas mice injected with MS382 or vehicle had no dysfunctions. Injection of FN075 into the substantia nigra revealed a significant loss of TH-positive neurons already at 3 months and TH-negative inclusion-like structures were detected in substantia nigra neurons of these mice. Thus, the results suggest that injection of a templator of α-synuclein aggregation into the brain of normal mice can serve as a novel experimental design for an animal model of Parkinson’s disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Parkinson's disease
- alpha-synuclein
- small molecules
- FN075
- MS382
- medicinsk utvecklings- och neurobiologi
- Developmental Neurosciences
Publikations- och innehållstyp
- vet (ämneskategori)
- ovr (ämneskategori)