Expression of Nicotinamide N-Methyltransferase (E.C. 2.1.1.1) in the Parkinsonian Brain

• Published in: Journal of neuropathology and experimental neurology Vol. 61; no. 2; pp. 111 - 124
• Main Authors: PARSONS, RICHARD B, SMITH, MARIE-LOUISE, WILLIAMS, ADRIAN C, WARING, ROSEMARY H, RAMSDEN, DAVID B
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Association of Neuropathologists, Inc 01.02.2002; Lippincott Williams & Wilkins; Oxford University Press
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Brain - cytology; Brain - enzymology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Humans; Immunohistochemistry; Liver - enzymology; Male; Medical sciences; Methyltransferases - genetics; Methyltransferases - metabolism; Middle Aged; Neurology; Neurons - enzymology; Nicotinamide N-Methyltransferase; Parkinson Disease - enzymology; Parkinson Disease - physiopathology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Spinal Cord - enzymology; Tissue Distribution; Cerebellum; Human; Immunohistochemistry; Nervous system diseases; Enzyme; Pathogenesis; Transferases; Parkinson disease; Cerebral disorder; Pathology; Locus niger; Methyltransferases; Central nervous system disease; Degenerative disease; Molecular biology; Extrapyramidal syndrome; Nicotinamide N-methyltransferase
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1093/jnen/61.2.111

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.