Expression of metallothionein-I, -II, and -III in Alzheimer disease and animal models of neuroinflammation.
In recent years it has become increasingly clear that the metallothionein (MT) family of proteins is important in neurobiology. MT-I and MT-II are normally dramatically up-regulated by neuroinflammation. Results for MT-III are less clear. MTs could also be relevant in human neuropathology. In Alzheimer disease (AD), a major neurodegenerative disease, clear signs of inflammation and oxidative stress were detected associated with amyloid plaques. Furthermore, the number of cells expressing apoptotic markers was also significantly increased in these plaques. As expected, MT-I and MT-II immunostaining was dramatically increased in cells surrounding the plaques, consistent with astrocytosis and microgliosis, as well as the increased oxidative stress elicited by the amyloid deposits. MT-III, in contrast, remained essentially unaltered, which agrees with some but not all studies, of AD. In situ hybridization results in a transgenic mouse model of AD amyloid deposits, the Tg2576 mouse, which expresses human Abeta precursor protein harboring the Swedish K670N/M671L mutations, are in accordance with results in human brains. Overall, these and other studies strongly suggest specific roles for MT-I, MT-II, and MT-III in brain physiology.
Hidalgo
Juan
J
Institute of Neurosciences, Department of Cellular Biology, Physiology and Immunology, Animal Physiology Unit, Faculty of Sciences, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain 08193. Juan.Hidalgo@uab.es
Penkowa
Milena
M
Espejo
Carmen
C
Martínez-Cáceres
Eva M
EM
Carrasco
Javier
J
Quintana
Albert
A
Molinero
Amalia
A
Florit
Sergi
S
Giralt
Mercedes
M
Ortega-Aznar
Arantxa
A
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D023421:Models, Animal; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger; D008668:Metallothionein