BDNF in Huntington’s Disease: Role in Pathogenesis and Treatment

Huntington’s Disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric abnormalities, and is inherited in an autosomal dominant fashion (Borrell-Pages et al., 2006). HD is caused by the CAG trinucleotide repeat expansion in the first exon of the gene encoding huntingtin (htt) (The Huntington's Disease Collaborative Research Group, 1993). This mutation is translated into a polyglutamine (poly Q) stretch near the amino terminus of htt, which results in a toxic gain of function (Gusella & MacDonald, 2000). Although htt is widely expressed in the human body and its mutation is not tissue-specific, the striatum is preferentially affected. The pathological changes in the striatum develop first in the caudate nucleus and then in the putamen, causing a 50-60% neuronal loss in these areas (Mann et al., 1993; Vonsattel & DiFiglia, 1998). Striatal atrophy is due to selective degeneration of medium-sized spiny neurons (MSNs), which comprise 90% of striatal neurons. Interestingly, the MSNs of the indirect pathway, responsible for inhibition of involuntary movement, are preferentially affected, causing motor symptoms of HD such as uncontrollable sequence of movements called “chorea”. In the course of the disease, atrophy spreads to other brain regions, including the cerebral cortex, the globus pallidus (GP), and the thalamus (Mann et al., 1993).