Evaluation of clinically relevant glutamate pathway inhibitors in in vitro model of Huntington's disease

Jun Wu; Tieshan Tang; Ilya Bezprozvanny

doi:10.1016/j.neulet.2006.08.036

Evaluation of clinically relevant glutamate pathway inhibitors in in vitro model of Huntington's disease

Jun Wu, Tieshan Tang, Ilya Bezprozvanny

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44 Scopus citations

Abstract

Huntington's disease (HD) is an autosomal dominant, inherited and fatal neurodegenerative disorder for which there is, at present, no effective treatment or cure. Striatal medium spiny neurons (MSN) are the most sensitive in HD. Dysregulation of glutamate/calcium signaling pathway emerges as a possible cause of striatal MSN neurodegeneration in HD. Here we evaluated five clinically relevant glutamate pathway inhibitors using previously developed in vitro HD model. We found that folic acid, gabapentin and lamotrigine did not protect HD neurons from glutamate-induced cell death, but memantine and riluzole were protective. Our results provide further support to potential use of memantine and riluzole for treatment of HD.

Original language	English (US)
Pages (from-to)	219-223
Number of pages	5
Journal	Neuroscience letters
Volume	407
Issue number	3
DOIs	https://doi.org/10.1016/j.neulet.2006.08.036
State	Published - Oct 30 2006

Keywords

Apoptosis
Calcium
Glutamate
Huntington's disease
Memantine
Riluzole
TUNEL
Transgenic mice

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/j.neulet.2006.08.036

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title = "Evaluation of clinically relevant glutamate pathway inhibitors in in vitro model of Huntington's disease",

abstract = "Huntington's disease (HD) is an autosomal dominant, inherited and fatal neurodegenerative disorder for which there is, at present, no effective treatment or cure. Striatal medium spiny neurons (MSN) are the most sensitive in HD. Dysregulation of glutamate/calcium signaling pathway emerges as a possible cause of striatal MSN neurodegeneration in HD. Here we evaluated five clinically relevant glutamate pathway inhibitors using previously developed in vitro HD model. We found that folic acid, gabapentin and lamotrigine did not protect HD neurons from glutamate-induced cell death, but memantine and riluzole were protective. Our results provide further support to potential use of memantine and riluzole for treatment of HD.",

keywords = "Apoptosis, Calcium, Glutamate, Huntington's disease, Memantine, Riluzole, TUNEL, Transgenic mice",

author = "Jun Wu and Tieshan Tang and Ilya Bezprozvanny",

note = "Funding Information: We thank Tianhua Lei for help with maintaining the YAC128 mouse colony and genotyping, Janet Young for administrative assistance, Michael Hayden for helpful discussions. We used information from Huntington's Outreach Project for Education, at Stanford (HOPES) to select glutamate pathway inhibitors for our studies. We would like to thank students and faculty who maintain HOPES. The study was supported by the Robert A. Welch Foundation, the HighQ foundation, and NINDS R01 NS38082. ",

year = "2006",

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doi = "10.1016/j.neulet.2006.08.036",

language = "English (US)",

volume = "407",

pages = "219--223",

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AU - Wu, Jun

AU - Tang, Tieshan

AU - Bezprozvanny, Ilya

N1 - Funding Information: We thank Tianhua Lei for help with maintaining the YAC128 mouse colony and genotyping, Janet Young for administrative assistance, Michael Hayden for helpful discussions. We used information from Huntington's Outreach Project for Education, at Stanford (HOPES) to select glutamate pathway inhibitors for our studies. We would like to thank students and faculty who maintain HOPES. The study was supported by the Robert A. Welch Foundation, the HighQ foundation, and NINDS R01 NS38082.

PY - 2006/10/30

Y1 - 2006/10/30

N2 - Huntington's disease (HD) is an autosomal dominant, inherited and fatal neurodegenerative disorder for which there is, at present, no effective treatment or cure. Striatal medium spiny neurons (MSN) are the most sensitive in HD. Dysregulation of glutamate/calcium signaling pathway emerges as a possible cause of striatal MSN neurodegeneration in HD. Here we evaluated five clinically relevant glutamate pathway inhibitors using previously developed in vitro HD model. We found that folic acid, gabapentin and lamotrigine did not protect HD neurons from glutamate-induced cell death, but memantine and riluzole were protective. Our results provide further support to potential use of memantine and riluzole for treatment of HD.

AB - Huntington's disease (HD) is an autosomal dominant, inherited and fatal neurodegenerative disorder for which there is, at present, no effective treatment or cure. Striatal medium spiny neurons (MSN) are the most sensitive in HD. Dysregulation of glutamate/calcium signaling pathway emerges as a possible cause of striatal MSN neurodegeneration in HD. Here we evaluated five clinically relevant glutamate pathway inhibitors using previously developed in vitro HD model. We found that folic acid, gabapentin and lamotrigine did not protect HD neurons from glutamate-induced cell death, but memantine and riluzole were protective. Our results provide further support to potential use of memantine and riluzole for treatment of HD.

KW - Apoptosis

KW - Calcium

KW - Glutamate

KW - Huntington's disease

KW - Memantine

KW - Riluzole

KW - TUNEL

KW - Transgenic mice

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ER -

Evaluation of clinically relevant glutamate pathway inhibitors in in vitro model of Huntington's disease

Abstract

Keywords

ASJC Scopus subject areas

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