TY - JOUR
T1 - Metallothionein in the central nervous system
T2 - Roles in protection, regeneration and cognition
AU - West, Adrian K.
AU - Hidalgo, Juan
AU - Eddins, Donnie
AU - Levin, Edward D.
AU - Aschner, Michael
N1 - Funding Information:
This work is supported by the Ministerio de Ciencia y Tecnología and Feder SAF2005-00671 and European Comission FP6 Integrated Project Exgenesis (Ref. LSHM-CT-2004-005272) (JH); PHS grants NIEHS 07331 (MA); Australia Alzheimer's Research and Australian Research Council (AKW); Autism Speaks and the Duke University Superfund Basic Research Center ES010356 (EDL and DE). Thanks to Ann Petro, Ninitia Pollard, Charles Perraut and Jonathan H. Freedman (EL) and the NeuroRepair Group, Menzies Research Institute and colleagues (AKW) for their valuable work on these projects.
PY - 2008/5
Y1 - 2008/5
N2 - Metallothionein (MT) is an enigmatic protein, and its physiological role remains a matter of intense study and debate 50 years after its discovery. This is particularly true of its function in the central nervous system (CNS), where the challenge remains to link its known biochemical properties of metal binding and free radical scavenging to the intricate workings of brain. In this compilation of four reports, first delivered at the 11th International Neurotoxicology Association (INA-11) Meeting, June 2007, the authors present the work of their laboratories, each of which gives an important insight into the actions of MT in the brain. What emerges is that MT has the potential to contribute to a variety of processes, including neuroprotection, regeneration, and even cognitive functions. In this article, the properties and CNS expression of MT are briefly reviewed before Dr Hidalgo describes his pioneering work using transgenic models of MT expression to demonstrate how this protein plays a major role in the defence of the CNS against neurodegenerative disorders and other CNS injuries. His group's work leads to two further questions, what are the mechanisms at the cellular level by which MT acts, and does this protein influence higher order issues of architecture and cognition? These topics are addressed in the second and third sections of this review by Dr West, and Dr Levin and Dr Eddins, respectively. Finally, Dr Aschner examines the ability of MT to protect against a specific toxicant, methylmercury, in the CNS.
AB - Metallothionein (MT) is an enigmatic protein, and its physiological role remains a matter of intense study and debate 50 years after its discovery. This is particularly true of its function in the central nervous system (CNS), where the challenge remains to link its known biochemical properties of metal binding and free radical scavenging to the intricate workings of brain. In this compilation of four reports, first delivered at the 11th International Neurotoxicology Association (INA-11) Meeting, June 2007, the authors present the work of their laboratories, each of which gives an important insight into the actions of MT in the brain. What emerges is that MT has the potential to contribute to a variety of processes, including neuroprotection, regeneration, and even cognitive functions. In this article, the properties and CNS expression of MT are briefly reviewed before Dr Hidalgo describes his pioneering work using transgenic models of MT expression to demonstrate how this protein plays a major role in the defence of the CNS against neurodegenerative disorders and other CNS injuries. His group's work leads to two further questions, what are the mechanisms at the cellular level by which MT acts, and does this protein influence higher order issues of architecture and cognition? These topics are addressed in the second and third sections of this review by Dr West, and Dr Levin and Dr Eddins, respectively. Finally, Dr Aschner examines the ability of MT to protect against a specific toxicant, methylmercury, in the CNS.
KW - Astrocyte
KW - Central nervous system
KW - Cognition
KW - Metallothionein
KW - Methylmercury
KW - Neuroprotection
KW - Regeneration
KW - Transgenic animal
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U2 - 10.1016/j.neuro.2007.12.006
DO - 10.1016/j.neuro.2007.12.006
M3 - Review article
C2 - 18313142
AN - SCOPUS:44649152946
SN - 0161-813X
VL - 29
SP - 489
EP - 503
JO - Neurotoxicology
JF - Neurotoxicology
IS - 3
ER -