Arches. Photo by Daniel Chia
HOPES: Huntington's Outreach Project for Education, at Stanford
Feb
03
2014

TRiC and Huntingtin Protein Aggregation

In Huntington’s disease (HD), an abnormal increase in the number of CAG repeats in the mutant Huntington gene corresponds to a long tract of glutamine amino acids in the huntingtin protein (Htt). This excessively long glutamine tract is sticky and leads to the formation of protein aggregates in brain cells. Whether these aggregates are toxic [...]

Oct
24
2013

Genome Editing

Although the pathology of Huntington’s disease (HD) is still not completely understood, we know that HD is a genetic disorder where the root cause of every HD case is a longer-than-normal series of three repeated DNA base pairs, CAG, in the HD gene. A DNA sequence provides the instructions for the cell to make mRNA [...]

Apr
04
2012

Gene Silencing

Huntington’s disease (HD) is a genetic disease due to the abnormal CAG expansion of the mutated huntingtin gene.  The mutated gene instructs cells in the body to produce a version of the huntingtin protein that ultimately leads to neuronal damage in the brain and creates the symptoms of HD.  Currently, available HD therapies can only [...]

Jun
26
2011

About Protein Aggregation

The altered huntingtin protein responsible for HD has been shown to contain many more molecules of the amino acid glutamine than regular huntingtin. This abundance of glutamine is due to repetitive copies of the CAG codon in the Huntington gene. The extended glutamine tracts of these proteins have affinity for one another, and tend to [...]

Jun
29
2010

Antisense Gene Therapy

Antisense gene therapy is a gene silencing technique similar to RNA interference, but uses a slightly different mechanism. The therapy is called a gene silencing technique because, instead of repairing the gene, it aims to “silence” the gene’s effect. Recall that people with Huntington’s disease (HD) have two copies, or alleles, of the Huntington gene, [...]

Jun
29
2010

Rapamycin

Drug summary: Rapamycin, also known as sirolimus, is an FDA-approved antibiotic and immunosuppressant. It is already being used in organ transplant patients and is currently being tested in phase II and III clinical trials in cancer patients for its antitumor activity. Rapamycin inhibits the activity of a protein called mTOR which, among its other functions, inhibits a process called autophagy

Jun
29
2010

Cystamine

Drug summary: Cystamine inhibits the activity of transglutaminase (TGase), an enzyme involved in the formation of of huntingtin of protein aggregates. Treating mouse models of HD with cystamine in several studies has resulted in improvements in physical symptoms and decreased nerve cell death. These results suggest that cystamine may have beneficial effects for people with HD.

Jun
29
2010

Trehalose

This chapter discusses a small molecule called trehalose that may help prevent protein aggregation. Everyone has a certain copy, or allele, of the Huntington gene, but people with Huntington’s disease (HD) have one copy that is longer than normal. The longer section of this HD allele consists of a repeated sequence, CAG, which codes for glutamine, an amino acid

Jun
29
2010

RNA Interference (RNAi)

People with Huntington’s disease have two different copies, or alleles, of the Huntington gene. As we discussed here, genes are sections of DNA that provide the information for making proteins. The non-HD allele produces a normally functioning protein, but the HD allele produces a protein that is either the cause or result of many problems [...]

Jun
29
2010

Geldanamycin

Drug Summary: Geldanamycin (GA) is a naturally-occurring drug produced by microorganisms to protect themselves from disease-causing substances. GA binds to a special kind of protein called a heat shock protein. All cells produce a common set of heat shock proteins (Hsp) in response to a variety of stresses, including heat, exposure to toxic compounds, or [...]