title: Expression of nicotinamide N-methyltransferase (E.C. 2.1.1.1) in the Parkinsonian brain.
abstract: Nicotinamide N-methyltransferase (NNMT) has been proposed as a link between the environmental and genetic factors of Parkinson disease (PD). Therefore, we explored the hypothesis that high levels of NNMT expression may predispose to the development of PD. Regions of high mRNA expression were shown in the spinal cord, medulla, and temporal lobe, with lowest expression in the cerebellum, subthalamic nucleus, and caudate nucleus. Using 2 NNMT antibodies, the protein was shown to be expressed in multipolar neurons in the temporal lobe, caudate nucleus, and spinal cord, granular neurons of the cerebellum, dopaminergic neurons in the substantia nigra, and in the axons of the third nerve. Expression of NNMT was compared in PD and non-PD control cerebella and caudate nucleus. PD tissue exhibited significantly increased levels of NNMT protein and activity. PD disease duration was inversely correlated with the level of expression in cerebellum. This is the first demonstration that patients with PD have higher levels of NNMT activity and protein in brain tissue than those without PD and that NNMT expression is associated with neurons that degenerate in PD.
authors.affiliation: Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, United Kingdom.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Parsons
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Smith
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Williams
authors.forename: Rosemary H
authors.initials: RH
authors.lastname: Waring
authors.forename: David B
authors.initials: DB
authors.lastname: Ramsden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000166:cytology / Q000201:enzymology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009474:Neurons / Q000201:enzymology*; D050903:Nicotinamide N-Methyltransferase; D010300:Parkinson Disease / Q000201:enzymology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000201:enzymology; D014018:Tissue Distribution
chemical_list: D012333:RNA, Messenger; D008780:Methyltransferases; C494406:NNMT protein, human; D050903:Nicotinamide N-Methyltransferase