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Expression of the proto-oncogene Ret, a component of the GDNF receptor complex, persists in human substantia nigra neurons in Parkinson's disease
- Source :
- Brain research. 792(2)
- Publication Year :
- 1998
-
Abstract
- The proto-oncogene Ret, a membrane-associated receptor protein tyrosine kinase, has recently been shown to be a component of the glial cell line-derived neurotrophic factor (GDNF) receptor complex. GDNF has potent dopaminergic neurotrophic properties and has been suggested as a treatment for Parkinson's disease (PD). In this study, tissue sections of human substantia nigra (SN) from normal and PD cases were examined to determine the pattern of Ret expression in this region, and whether there was continued Ret expression in surviving dopaminergic neurons in PD cases. Using a polyclonal antibody to the amino terminal of Ret, immunoreactivity was localized in the SN to dopaminergic neurons. The antibody predominantly identified punctate deposits within cells. A similar pattern of immunoreactivity was observed in rat and monkey SN neurons. In neurologically normal cases, immunoreactivity was detected in many of the SN neurons. In all the PD cases studied, continued expression of Ret was observed in many of the surviving dopaminergic neurons. In certain cases, it was also detected on cells with the morphology of microglia. Ret expression by microglia was confirmed by immunoblot analysis on the human THP-1 macrophage type cell line. However, these cells did not express the mRNA for GDNFRalpha, the other component of the GDNF receptor complex.
- Subjects :
- Adult
Male
medicine.medical_specialty
Receptor complex
Glial Cell Line-Derived Neurotrophic Factor Receptors
Dopamine
Oncogene RET
Immunoblotting
Gene Expression
Substantia nigra
Biology
Proto-Oncogene Mas
Monocytes
Cell Line
Rats, Sprague-Dawley
Neurotrophic factors
Internal medicine
Proto-Oncogene Proteins
Glial cell line-derived neurotrophic factor
medicine
Animals
Drosophila Proteins
Humans
RNA, Messenger
Molecular Biology
Aged
Aged, 80 and over
Neurons
General Neuroscience
Proto-Oncogene Proteins c-ret
Receptor Protein-Tyrosine Kinases
Parkinson Disease
Middle Aged
Protein-Tyrosine Kinases
Molecular biology
Immunohistochemistry
Rats
Substantia Nigra
Endocrinology
nervous system
biology.protein
Female
Neurology (clinical)
GDNF family of ligands
Developmental Biology
Neurotrophin
Subjects
Details
- ISSN :
- 00068993
- Volume :
- 792
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Brain research
- Accession number :
- edsair.doi.dedup.....63805d6d8ab8c53e70d94ce9e1bd83cb