Molecular Neurobiology

, Volume 43, Issue 1, pp 1–11

Huntington’s Disease and Group I Metabotropic Glutamate Receptors

  • Fabiola M. Ribeiro
  • Rita G. W. Pires
  • Stephen S. G. Ferguson
Article

DOI: 10.1007/s12035-010-8153-1

Cite this article as:
Ribeiro, F.M., Pires, R.G.W. & Ferguson, S.S.G. Mol Neurobiol (2011) 43: 1. doi:10.1007/s12035-010-8153-1

Abstract

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder characterized by involuntary body movement, cognitive impairment and psychiatric disturbance. A polyglutamine expansion in the amino-terminal region of the huntingtin (htt) protein is the genetic cause of HD. Htt protein interacts with a wide variety of proteins, and htt mutation causes cell signaling alterations in various neurotransmitter systems, including dopaminergic, glutamatergic, and cannabinoid systems, as well as trophic factor systems. This review will overview recent findings concerning htt-promoted alterations in cell signaling that involve different neurotransmitters and trophic factor systems, especially involving mGluR1/5, as glutamate plays a crucial role in neuronal cell death. The neuronal cell death that takes place in the striatum and cortex of HD patients is the most important factor underlying HD progression. Metabotropic glutamate receptors (mGluR1 and mGluR5) have a very controversial role in neuronal cell death and it is not clear whether mGluR1/5 activation either protects or exacerbates neuronal death. Thus, understanding how mutant htt protein affects glutamatergic receptor signaling will be essential to further establish a role for glutamate receptors in HD and develop therapeutic strategies to treat HD.

Keywords

Huntington’s disease htt protein Metabotropic glutamate receptor (mGluR) 

Abbreviations

DHPG

(S)-3,5-dihydroxylphenylglycine

AMPA

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

CNS

Central nervous system

PLC

Phospholipase C

ERK

Extracellular signal-regulated kinase

MAPK

Mitogen-activated protein kinase

GPCR

G protein-coupled receptor

InsP

Inositol phosphate

AD

Alzheimer’s disease

HD

Huntington’s disease

htt

Huntingtin protein

IP3

Inositol-1,4,5-triphosphate

mGluR

Metabotropic glutamate receptor

NMDAR

N-methyl-d-aspartate receptor

PKC

Protein kinase C

PLCβ1

Phospholipase Cβ1

PLD

Phospholipase D

PLA2

Phospholipase A2

PI3K

Phosphoinositide 3-kinase

PDK1

Phosphoinositide-dependent kinase

PIKE

PI3K enhancer

MSNs

Medium-sized spiny neurons

PPE

Preproenkephalin

DARPP-32

Dopamine and cyclic AMP-regulated phosphoprotein, 32 kDa

GSK-3

Glycogen synthase kinase-3

EC

Endocannabinoid

BDNF

Brain-derived neurotrophic factor

AEA

Anandamide

2-AG

2- arachidonoyl glycerol

TRPV1

Transient receptor potential vanilloid 1

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Fabiola M. Ribeiro
    • 1
  • Rita G. W. Pires
    • 2
  • Stephen S. G. Ferguson
    • 3
  1. 1.Departamento de Bioquimica e Imunologia, ICBUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  2. 2.Departamento de Ciencias Fisiologicas, CCSUniversidade Federal do Espirito SantoVitoriaBrazil
  3. 3.J. Allyn Taylor Centre for Cell Biology, Molecular Brain Research Group, Robarts Research Institute and Department of Physiology and PharmacologyUniversity of Western OntarioLondonCanada

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