Evaluation of clinically relevant glutamate pathway inhibitors in in vitro model of Huntington's disease.
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.
Wu
Jun
J
Department of Physiology, UT Southwestern Medical Center at Dallas, TX, USA.
Tang
Tieshan
T
Bezprozvanny
Ilya
I
D000588:Amines / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005492:Folic Acid / Q000494:pharmacology; D000077206:Gabapentin; D018698:Glutamic Acid / Q000494:pharmacology / Q000502:physiology*; D006816:Huntington Disease / Q000188:drug therapy / Q000473:pathology*; D000077213:Lamotrigine; D008297:Male; D008559:Memantine / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019782:Riluzole / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D014227:Triazines; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D019782:Riluzole; D005492:Folic Acid; D000077213:Lamotrigine; D008559:Memantine