Retention of the cyanobacterial neurotoxin beta-N-methylamino-l-alanine in melanin and neuromelanin-containing cells--a possible link between Parkinson-dementia complex and pigmentary retinopathy.
beta-N-methylamino-l-alanine (BMAA), a neurotoxic amino acid produced by cyanobacteria, has been suggested to be involved in the etiology of a neurodegenerative disease complex which includes Parkinson-dementia complex (PDC). In PDC, neuromelanin-containing neurons in substantia nigra are degenerated. Many PDC patients also have an uncommon pigmentary retinopathy. The aim of this study was to investigate the distribution of (3)H-BMAA in mice and frogs, with emphasis on pigment-containing tissues. Using autoradiography, a distinct retention of (3)H-BMAA was observed in melanin-containing tissues such as the eye and neuromelanin-containing neurons in frog brain. Analysis of the binding of (3)H-BMAA to Sepia melanin in vitro demonstrated two apparent binding sites. In vitro-studies with synthetic melanin revealed a stronger interaction of (3)H-BMAA with melanin during synthesis than the binding to preformed melanin. Long-term exposure to BMAA may lead to bioaccumulation in melanin- and neuromelanin-containing cells causing high intracellular levels, and potentially changed melanin characteristics via incorporation of BMAA into the melanin polymer. Interaction of BMAA with melanin may be a possible link between PDC and pigmentary retinopathy.
Karlsson
Oskar
O
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Berg
Cecilia
C
Brittebo
Eva B
EB
Lindquist
Nils Gunnar
NG
D000599:Amino Acids, Diamino / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D000458:Cyanobacteria; D000087522:Cyanobacteria Toxins; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism*; D005123:Eye / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D011896:Rana temporaria; D012174:Retinitis Pigmentosa / Q000378:metabolism*; D049833:Sepia / Q000378:metabolism
D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D018690:Excitatory Amino Acid Agonists; D008543:Melanins; C014121:neuromelanin; C001824:beta-N-methylamino-L-alanine