RGD Reference Report - Influences of dopaminergic lesion on epidermal growth factor-ErbB signals in Parkinson's disease and its model: neurotrophic implication in nigrostriatal neurons. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Influences of dopaminergic lesion on epidermal growth factor-ErbB signals in Parkinson's disease and its model: neurotrophic implication in nigrostriatal neurons.

Authors: Iwakura, Y  Piao, YS  Mizuno, M  Takei, N  Kakita, A  Takahashi, H  Nawa, H 
Citation: Iwakura Y, etal., J Neurochem. 2005 May;93(4):974-83.
RGD ID: 2289955
Pubmed: PMID:15857400   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1471-4159.2005.03073.x   (Journal Full-text)

Epidermal growth factor (EGF) is a member of a structurally related family containing heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor alpha (TGFalpha) that exerts neurotrophic activity on midbrain dopaminergic neurons. To examine neurotrophic abnormality in Parkinson's disease (PD), we measured the protein content of EGF, TGFalpha, and HB-EGF in post-mortem brains of patients with Parkinson's disease and age-matched control subjects. Protein levels of EGF and tyrosine hydroxylase were decreased in the prefrontal cortex and the striatum of patients. In contrast, HB-EGF and TGFalpha levels were not significantly altered in either region. The expression of EGF receptors (ErbB1 and ErbB2, but not ErbB3 or ErbB4) was down-regulated significantly in the same forebrain regions. The same phenomenon was mimicked in rats by dopaminergic lesions induced by nigral 6-hydroxydopamine infusion. EGF and ErbB1 levels in the striatum of the PD model were markedly reduced on the lesioned side, compared with the control hemisphere. Subchronic supplement of EGF in the striatum of the PD model locally prevented the dopaminergic neurodegeration as measured by tyrosine hydroxylase immunoreactivity. These findings suggest that the neurotrophic activity of EGF is maintained by afferent signals of midbrain dopaminergic neurons and is impaired in patients with Parkinson's disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Parkinson's disease  IEP 2289955; 2289955protein:decreased expression:forebrainRGD 
Parkinson's disease  ISOEGFR (Homo sapiens)2289955; 2289955protein:decreased expression:forebrainRGD 
Parkinson's disease  ISOERBB2 (Homo sapiens)2289955; 2289955protein:decreased expression:forebrainRGD 
Parkinson's disease  IEP 2289955protein:decreased expression:striatum (human)RGD 
Parkinson's disease  ISOTH (Homo sapiens)2289955; 2289955protein:decreased expression:striatum (human)RGD 
Parkinsonism  ISOEgfr (Rattus norvegicus)2289955; 2289955protein:decreased expression:striatumRGD 
Parkinsonism  IEP 2289955protein:decreased expression:striatumRGD 

Objects Annotated

Genes (Rattus norvegicus)
Egfr  (epidermal growth factor receptor)
Erbb2  (erb-b2 receptor tyrosine kinase 2)
Th  (tyrosine hydroxylase)

Genes (Mus musculus)
Egfr  (epidermal growth factor receptor)
Erbb2  (erb-b2 receptor tyrosine kinase 2)
Th  (tyrosine hydroxylase)

Genes (Homo sapiens)
EGFR  (epidermal growth factor receptor)
ERBB2  (erb-b2 receptor tyrosine kinase 2)
TH  (tyrosine hydroxylase)


Additional Information