PMID- 22306345
OWN - NLM
STAT- MEDLINE
DCOM- 20130211
LR  - 20120907
IS  - 1872-9754 (Electronic)
IS  - 0197-0186 (Linking)
VI  - 61
IP  - 4
DP  - 2012 Sep
TI  - Metabotropic glutamate receptors in neurodegeneration/neuroprotection: still a 
      hot topic?
PG  - 559-65
LID - 10.1016/j.neuint.2012.01.017 [doi]
AB  - Moving from early studies, we here review the most recent evidence linking 
      metabotropic glutamate (mGlu) receptors to processes of 
      neurodegeneration/neuroprotection. The use of knockout mice and subtype-selective 
      drugs has increased our knowledge of the precise role played by individual mGlu 
      receptor subtypes in these processes. Activation of mGlu1 and mGlu5 receptors may 
      either amplify or reduce neuronal damage depending on the context and the nature 
      of the toxic insults. In contrast, mGlu1 and mGlu5 receptors antagonists are 
      consistently protective in in vitro and in vivo models of neuronal death. A 
      series of studies suggest that mGlu1 receptor antagonists or negative allosteric 
      modulators (NAMs) are promising candidates for the treatment of ischemic brain 
      damage, whereas mGlu5 receptor NAMs, which have been clinically developed for the 
      treatment of Parkinson's disease (PD) and l-DOPA-induced dyskinesias, protect 
      nigro-striatal dopaminergic neurons against 
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity in mice and monkeys. 
      Activation of glial mGlu3 receptors promotes the formation of various 
      neurotrophic factors, such as transforming growth factor-beta (TGF-beta), glial-derived 
      neurotrophic factor (GDNF), nerve growth factor (NGF), and brain-derived 
      neurotrophic factor (BDNF). Hence, selective mGlu3 receptor agonists or positive 
      allosteric modulators (PAMs) (not yet available) are potentially helpful in the 
      treatment of chronic neurodegenerative disorders such as PD, Alzheimer's disease 
      (AD), and amyotrophic lateral sclerosis. Selective mGlu2 receptor PAMs should be 
      used with caution in AD patients because these drugs are shown to amplify 
      beta-amyloid neurotoxicity. Finally, mGlu4 receptor agonists/PAMs share with mGlu5 
      receptor NAMs the ability to improve motor symptoms associated with PD and 
      attenuate nigro-striatal degeneration at the same time. No data are yet available 
      on the role of mGlu7 and mGlu8 receptors in neurodegeneration/neuroprotection.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Caraci, Filippo
AU  - Caraci F
AD  - Department of Formative Processes, University of Catania, Catania, Italy.
FAU - Battaglia, Giuseppe
AU  - Battaglia G
FAU - Sortino, Maria Angela
AU  - Sortino MA
FAU - Spampinato, Simona
AU  - Spampinato S
FAU - Molinaro, Gemma
AU  - Molinaro G
FAU - Copani, Agata
AU  - Copani A
FAU - Nicoletti, Ferdinando
AU  - Nicoletti F
FAU - Bruno, Valeria
AU  - Bruno V
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20120125
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptors, Metabotropic Glutamate)
SB  - IM
MH  - Allosteric Regulation
MH  - Animals
MH  - Haplorhini
MH  - Mice
MH  - Neuroprotective Agents/pharmacology
MH  - Receptors, Metabotropic Glutamate/*metabolism
EDAT- 2012/02/07 06:00
MHDA- 2013/02/12 06:00
CRDT- 2012/02/07 06:00
PHST- 2011/12/30 00:00 [received]
PHST- 2012/01/14 00:00 [revised]
PHST- 2012/01/14 00:00 [accepted]
PHST- 2012/02/07 06:00 [entrez]
PHST- 2012/02/07 06:00 [pubmed]
PHST- 2013/02/12 06:00 [medline]
AID - S0197-0186(12)00029-0 [pii]
AID - 10.1016/j.neuint.2012.01.017 [doi]
PST - ppublish
SO  - Neurochem Int. 2012 Sep;61(4):559-65. doi: 10.1016/j.neuint.2012.01.017. Epub 
      2012 Jan 25.