Targeting glutamate mediated excitotoxicity in huntington's disease: Neural progenitors and partial glutamate antagonist - Memantine

被引：22

作者：

Anitha, M. ^{[1
]}

Nandhu, M. S. ^{[1
]}

Anju, T. R. ^{[1
]}

Jes, P. ^{[1
]}

Paulose, C. S. ^{[1
]}

机构：

[1] Cochin Univ Sci & Technol, Dept Biotechnol, Ctr Neurosci, Mol Neurobiol & Cell Biol Unit, Cochin 682022, Kerala, India

来源：

MEDICAL HYPOTHESES | 2011年 / 76卷 / 01期

关键词：

TRANSGENIC MOUSE MODEL;

D O I：

10.1016/j.mehy.2010.09.003

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Huntington's disease (HD) is a fatal progressive neurodegenerative disorder with autosomal dominant inheritance. In humans mutated huntingtin (htt) induces a preferential loss of medium spiny neurons (MSN) of the striatum and causes motor, cognitive and emotional deficits. One of the proposed cellular mechanism underlying medium spiny neurons degeneration is excitotoxic pathways mediated by glutamate receptors. The hypothesis proposed is restoration of medium spiny neurons in Huntington's disease using neural progenitor cell implantation and attenuation of glutamate mediated excitotoxicity using a partial glutamate antagonist - Memantine. Memantine can block the NMDA receptors and will prevent excess calcium influx into the neurons decreases the vulnerability of medium spiny neurons to glutamate mediated excitotoxicity. Neural progenitor cell implantation can enhance endogenous neurogenesis process replacing the degenerated medium spiny neurons in the striatum. This has immense significance in the management of Huntington's disease. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：138 / 140

页数：3

共 18 条

[1] Altered cortical glutamate receptor function in the r6/2 model of Huntington's disease [J].

André, VM ;

Cepeda, C ;

Venegas, A ;

Gomez, Y ;

Levine, MS .

JOURNAL OF NEUROPHYSIOLOGY, 2006, 95 (04) :2108-2119

[2]

BOLAM JP, 1988, EXP BRAIN RES, V70, P361

[3]

Bolam JP., 2006, Microcircuits: The Interface Between Neurons and Global Brain Function, P165

[4] Frontal-striatal disconnection disrupts cognitive performance of the frontal-type in the rat [J].

Dunnett, SB ;

Meldrum, A ;

Muir, JL .

NEUROSCIENCE, 2005, 135 (04) :1055-1065

[5] Altered NMDA receptor trafficking in a yeast artificial chromosome transgenic mouse model of Huntington's disease [J].

Fan, Mannie M. Y. ;

Fernandes, Herman B. ;

Zhang, Lily Y. J. ;

Hayden, Michael R. ;

Raymond, Lynn A. .

JOURNAL OF NEUROSCIENCE, 2007, 27 (14) :3768-3779

[6] EVIDENCE FOR DEGENERATIVE AND REGENERATIVE CHANGES IN NEOSTRIATAL SPINY NEURONS IN HUNTINGTONS-DISEASE [J].

GRAVELAND, GA ;

WILLIAMS, RS ;

DIFIGLIA, M .

SCIENCE, 1985, 227 (4688) :770-773

[7] Metabotropic glutamate receptors and striatal synaptic plasticity: implications for neurological diseases [J].

Gubellini, P ;

Pisani, A ;

Centonze, D ;

Bernardi, G ;

Calabresi, P .

PROGRESS IN NEUROBIOLOGY, 2004, 74 (05) :271-300

[8] The use of transgenic and knock-in mice to study Huntington's disease [J].

Hickey, MA ;

Chesselet, MF .

CYTOGENETIC AND GENOME RESEARCH, 2003, 100 (1-4) :276-286

[9] Huntingtin and the molecular pathogenesis of Huntington's disease - Fourth in molecular medicine review series [J].

Landles, C ;

Bates, GP .

EMBO REPORTS, 2004, 5 (10) :958-963

[10] D1 AND D2 DOPAMINE-RECEPTOR GENE-EXPRESSION IN THE RAT STRIATUM - SENSITIVE CRNA PROBES DEMONSTRATE PROMINENT SEGREGATION OF D1 AND D2 MESSENGER-RNAS IN DISTINCT NEURONAL POPULATIONS OF THE DORSAL AND VENTRAL STRIATUM [J].

LEMOINE, C ;

BLOCH, B .

JOURNAL OF COMPARATIVE NEUROLOGY, 1995, 355 (03) :418-426

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