NPT520-34 improves neuropathology and motor deficits in a transgenic mouse model of Parkinson's disease.
Brain
; 144(12): 3692-3709, 2021 12 31.
Article
en En
| MEDLINE
| ID: mdl-34117864
ABSTRACT
NPT520-34 is a clinical stage, small molecule being developed for the treatment of Parkinson's disease and other neurodegenerative disorders. The therapeutic potential of NPT520-34 was first suggested by findings from cell-based assays of alpha-synuclein clearance. As reported here, NPT520-34 was subsequently evaluated for therapeutically relevant actions in a transgenic animal model of Parkinson's disease that overexpresses human alpha-synuclein and in an acute lipopolysaccharide-challenge model using wild-type mice. Daily administration of NPT520-34 to mThy1-alpha-synuclein (Line 61) transgenic mice for 1 or 3 months resulted in reduced alpha-synuclein pathology, reduced expression of markers of neuroinflammation, and improvements in multiple indices of motor function. In a lipopolysaccharide-challenge model using wild-type mice, a single dose of NPT520-34 reduced lipopolysaccharide-evoked increases in the expression of several pro-inflammatory cytokines in plasma. These findings demonstrate the beneficial effects of NPT520-34 on both inflammation and protein-pathology end points, with consequent improvements in motor function in an animal model of Parkinson's disease. These findings further indicate that NPT520-34 may have two complementary actions (i) to increase the clearance of neurotoxic protein aggregates; and (ii) to directly attenuate inflammation. NPT520-34 treatment may thereby address two of the predominate underlying pathophysiological aspects of neurodegenerative disorders such as Parkinson's disease.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
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Fármacos Neuroprotectores
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Trastornos Parkinsonianos
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Actividad Motora
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article