Therapeutic perspectives for the treatment of Huntington's disease: treating the whole body.
Huntington's disease (HD) is a tremendously debilitating disorder that strikes relatively young individuals and progresses rapidly over the next ten to fifteen years inducing a loss of cognitive and motor skills and eventually death occurs. The primary locus of the disorder is a polyglutamine expansion of the protein product of the huntingtin (htt) gene. The htt protein appears to be a scaffolding protein that orchestrates the complex assembly of multiple intracellular proteins involved in multiple processes, including vesicular movement and cell metabolism. The htt protein is ubiquitously expressed in human tissues but the predominance of the interest in the pathology lies in its effects on the central nervous system (CNS). Most of the current therapeutics for HD thus have been targeted at preventing neuronal damage in the CNS, however, a considerable body of evidence has been accumulating to suggest that the maintenance of a healthy nervous system is tightly linked with peripheral physiological health. Therefore treatment of both the peripheral and central pathophysiologies of HD could form the basis of a more effective HD therapeutic strategy.
Martin
Bronwen
B
National Institute on Aging, NIH, Gerontology Research Center, Baltimore, MD 21224, USA.
Golden
Erin
E
Keselman
Alex
A
Stone
Matthew
M
Mattson
Mark P
MP
Egan
Josephine M
JM
Maudsley
Stuart
S
D000818:Animals; D002490:Central Nervous System; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D017933:Peripheral Nervous System; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins