Advances in Zebrafish as a Comprehensive Model of Mental Disorders

Figure 9

Pathogenetic mechanisms of Huntington’s disease. (a) Huntington’s disease is an inherited neurodegenerative disorder, associated with an expanded polyglutamine (poly Q) region in the protein encoded by the huntingtin (HTT) gene. (b) In response to proteolytic enzymes, the full-length native huntingtin protein is cleaved to produce additional protein fragments. (c) HTT exon1 and other fragments are transferred to the nucleus. (d) After aggregation, these proteins format inclusions in the nucleus. (e) Huntingtin fragments oligomerize and aggregate. (f) Disease-related disruption of the proteostasis network accelerates huntingtin aggregation. (g) The aberrant of huntingtin results in cellular impairments, including synaptic dysfunction, mitochondrial toxicity, and a decreased rate of axonal transport. Reproduced with permission from [310].