期刊
JOURNAL OF NEUROCHEMISTRY
卷 117, 期 6, 页码 1066-1074出版社
WILEY
DOI: 10.1111/j.1471-4159.2011.07284.x
关键词
dopamine; ErbB4 receptor; neuregulin; neuroprotection; Parkinson's disease
资金
- German Ministry of Research and Technology [BMBF-Biochance4 0315123]
- German National Genome Research Network [01GS08136-4]
- European Community [220656]
- University Clinics Giessen and Marburg (UKGM)
P>Neuregulin-1 (Nrg1) is genetically linked to schizophrenia, a disease caused by neurodevelopmental imbalance in dopaminergic function. The Nrg1 receptor ErbB4 is abundantly expressed on midbrain dopaminergic neurons. Nrg1 has been shown to penetrate blood-brain barrier, and peripherally administered Nrg1 activates ErbB4 and leads to a persistent hyperdopaminergic state in neonatal mice. These data prompted us to study the effect of peripheral administration of Nrg1 in the context of Parkinson's disease, a neurodegenerative disorder affecting the dopaminergic system in the adult brain. We observed that systemic injections of the extracellular domain of Nrg1 beta(1) (Nrg1 beta(1)-ECD) increased dopamine levels in the substantia nigra and striatum of adult mice. Nrg1 beta(1)-ECD injections also significantly protected the mouse nigrostriatal dopaminergic system morphologically and functionally against 6-hydroxydopamine-induced toxicity in vivo. Moreover, Nrg1 beta(1)-ECD also protected human dopaminergic neurons in vitro against 6-hydroxydopamine. In conclusion, we have identified Nrg1 beta(1)-ECD as a neurotrophic factor for adult mouse and human midbrain dopaminergic neurons with peripheral administratability, warranting further investigation as therapeutic option for Parkinson's disease patients.
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