6 ms·

Interesting comment from the original article. I would appreciate if anyone could more simply explain what these 8 diseases have in common: "9. Kelvin Stott on

Interesting comment from the original article. I would appreciate if anyone could more simply explain what these 8 diseases have in common: "9. Kelvin Stott on March 28, 2014 11:57 AM writes... I did my PhD on the molecular mechanism of HD with Nobel laureate Max Perutz back in 1993-6. We were trying to testing his "polar zipper" hypothesis, whereby expanded glutamine repeats aggregate into extended b-sheets that are inherently toxic, much like other amyoid-related diseases. And in fact, the mutant protein has been shown to form non-specific pores in cell membranes, just like other amyloid proteins. That was many years ago, but anyway, I'd still like to share my perspective on this... The problem I see with the mechanism proposed in this Nature paper is seems too specific for HD and huntingtin, however at least SEVEN other neurodegenerative diseases (SCA1, SCA2, SCA3/MJD, DRPLA, Kennedy's Disease, SBMA, etc.) have been linked to the expansion of glutamine repeats in completely unrelated proteins. To me this is just too much of a coincidence for each disease to be explained by a different mechanism, and I think any mechanism for HD must be shown to occur in all these other diseases before I would be prepared to believe it. Just my 2c."

jamessb 13y ago
They are all caused by additional repeats of the DNA sequence 'CAG' in a gene. This causes additional copies of the amino-acid glutamine to be inserted into the corresponding protein. Consequently, Bad Things happen (eg. the protein molecules aggregate into insoluble complexes), resulting in disease. The specific protein that is affected depends on the disease (huntingtin, ataxin-1, ataxin-2, ataxin-3, ATN1, and the androgen receptor for Huntington's, SCA1, SCA2, SCA3/MJD, DRPLA, Kennedy's Disease, and SBMA, respectively). The best reference for genetic diseases is the Online Mendelian Inheritance in Man database: http://omim.org/ http://omim.org/
refurb 13y ago
The author of that comment is just saying that several other neurodegenerative diseases (the 7 he listed) are so similar to Huntington's disease in terms of disease progression and genetic traits (the glutamine repeats) that it seems unlikely that the glutamine repeats in Huntington's act through a specific enzyme, where for the other seven diseases the toxicity is due to amyloid formation (and the resulting impact via pore formation in membranes).

jamessb 13y ago

They are all caused by additional repeats of the DNA sequence 'CAG' in a gene. This causes additional copies of the amino-acid glutamine to be inserted into the corresponding protein. Consequently, Bad Things happen (eg. the protein molecules aggregate into insoluble complexes), resulting in disease. The specific protein that is affected depends on the disease (huntingtin, ataxin-1, ataxin-2, ataxin-3, ATN1, and the androgen receptor for Huntington's, SCA1, SCA2, SCA3/MJD, DRPLA, Kennedy's Disease, and SBMA, respectively). The best reference for genetic diseases is the Online Mendelian Inheritance in Man database: http://omim.org/ http://omim.org/

refurb 13y ago

The author of that comment is just saying that several other neurodegenerative diseases (the 7 he listed) are so similar to Huntington's disease in terms of disease progression and genetic traits (the glutamine repeats) that it seems unlikely that the glutamine repeats in Huntington's act through a specific enzyme, where for the other seven diseases the toxicity is due to amyloid formation (and the resulting impact via pore formation in membranes).