Metallothionein-I+II in neuroprotection.
Metallothionein (MT)-I+II synthesis is induced in the central nervous system (CNS) in response to practically any pathogen or disorder, where it is increased mainly in reactive glia. MT-I+II are involved in host defence reactions and neuroprotection during neuropathological conditions, in which MT-I+II decrease inflammation and secondary tissue damage (oxidative stress, neurodegeneration, and apoptosis) and promote post-injury repair and regeneration (angiogenesis, neurogenesis, neuronal sprouting and tissue remodelling). Intracellularly the molecular MT-I+II actions involve metal ion control and scavenging of reactive oxygen species (ROS) leading to cellular redox control. By regulating metal ions, MT-I+II can control metal-containing transcription factors, zinc-finger proteins and p53. However, the neuroprotective functions of MT-I+II also involve an extracellular component. MT-I+II protects the neurons by signal transduction through the low-density lipoprotein family of receptors on the cell surface involving lipoprotein receptor-1 (LRP1) and megalin (LRP2). In this review we discuss the newest data on cerebral MT-I+II functions following brain injury and experimental autoimmune encephalomyelitis.
Pedersen
Mie Ø
MØ
Section of Neuroprotection, Institute of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Jensen
Rikke
R
Pedersen
Dan S
DS
Skjolding
Anders D
AD
Hempel
Casper
C
Maretty
Lasse
L
Penkowa
Milena
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000503:physiopathology; D004660:Encephalitis / Q000517:prevention & control; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology; D004921:Erythropoietin / Q000502:physiology; D006801:Humans; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000502:physiology; D008668:Metallothionein / Q000096:biosynthesis / Q000502:physiology*; D009103:Multiple Sclerosis / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D018696:Neuroprotective Agents; D018384:Oxidative Stress / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction
D026561:Low Density Lipoprotein Receptor-Related Protein-2; D018696:Neuroprotective Agents; D011956:Receptors, Cell Surface; C109611:metallothionein receptor; D004921:Erythropoietin; D008668:Metallothionein