title: Expression of the proto-oncogene Ret, a component of the GDNF receptor complex, persists in human substantia nigra neurons in Parkinson's disease.
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.
authors.affiliation: Kinsmen Laboratory of Neurological Research and Neurodegenerative Disease Centre, University of British Columbia, Vancouver, BC, Canada. douglas_walker@bc.sympatico.ca
authors.forename: D G
authors.initials: DG
authors.lastname: Walker
authors.forename: T G
authors.initials: TG
authors.lastname: Beach
authors.forename: R
authors.initials: R
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Lile
authors.forename: K D
authors.initials: KD
authors.lastname: Beck
authors.forename: E G
authors.initials: EG
authors.lastname: McGeer
authors.forename: P L
authors.initials: PL
authors.lastname: McGeer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002460:Cell Line; D004298:Dopamine / Q000502:physiology; D029721:Drosophila Proteins; D005260:Female; D015870:Gene Expression / Q000502:physiology; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D009474:Neurons / Q000737:chemistry; D010300:Parkinson Disease / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis* / Q000235:genetics*; D013378:Substantia Nigra / Q000737:chemistry* / Q000166:cytology / Q000201:enzymology
chemical_list: D029721:Drosophila Proteins; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C495001:Ret protein, rat; D004298:Dopamine