Paroxetine retards disease onset and progression in Huntingtin mutant mice.
We report that administration of paroxetine, a widely prescribed antidepressant drug that acts by inhibiting reuptake of the neurotransmitter serotonin, suppresses the neurodegenerative process and increases the survival of huntingtin mutant mice, an animal model of Huntington's disease (HD). Paroxetine attenuated motor dysfunction and body weight loss and improved glucose metabolism in the HD mice. Paroxetine was beneficial when treatment was initiated before or after the onset of motor dysfunction, suggesting a potential for such antidepressant drugs in the treatment of presymptomatic and symptomatic HD patients.
Duan
Wenzhen
W
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, NIH, Baltimore, MD 21224, USA. duanwe@grc.nia.nih.gov
Guo
Zhihong
Z
Jiang
Haiyang
H
Ladenheim
Bruce
B
Xu
Xiangru
X
Cadet
Jean Lud
JL
Mattson
Mark P
MP
D000818:Animals; D018450:Disease Progression; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009687:Nuclear Proteins / Q000235:genetics*; D017374:Paroxetine / Q000494:pharmacology / Q000627:therapeutic use*
C086055:HTT protein, human; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009687:Nuclear Proteins; D017374:Paroxetine