A Huntington's Breakthrough? | Hacker News Reader

A Huntington's Breakthrough?

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52 pointsmhb12 comments

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."

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).

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/

grandpa has HD, dad has HD, and likely I will as well. Maybe someday we won't have to worry about this disease :(...

>>If I knew someone with the Huntingtin mutation, I believe that I would tell them to waste no time taking cysteine supplements

Based on this finding are you going to take cysteine supplements?

Do you know if cysteine supplements have side effects?

I hope so. My mom and grandmother had it which also puts me at risk.

Rule of the news, is there a question mark in the headline title? The answer is always no.

Does not apply. This is not a news article per se, but a blog post. :)

It's a known reputable source. The fact that it is also a blog, is not truly related to that.

"Snyder is proposing this as the actual mechanism of Huntington's, and they have shown, in human tissue culture and in mouse models of the disease, that supplementation with extra cysteine can stop or reverse the cellular signs of the disease."

Question mark or no, that sounds pretty positive. Anything that moves the eight ball on understanding the mechanism of a disease is good news.

Betteridge's law of headlines seems to be less commonly true than the law that if there's an article posted on HN with a question mark at the end then someone will inevitably dismiss it by citing Betteridge's law.

Maybe you should read the article. The answer is definitely not no.

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