more research

[stu2742]

I'm not sure if this has already been posted but very interesting research...stu

Dynamics Behind Neurological Disease?

ScienceDaily (Oct. 13, 2009) — Researchers at Lund University, Sweden, have taken a snapshot of proteins changing shape, sticking together and creating structures that are believed to trigger deadly processes in the nervous system. The discovery opens the possibility of designing drugs for a devastating neurological disease, ALS.

Research indicates that ALS, in common with other neurological disorders, such as Alzheimer's and Parkinson's disease, is caused by our own proteins, which form aberrant aggregates that are fatally toxic to our nerve cells. However, it has not been known what causes these proteins to aggregate. Researchers at Lund University have now revealed what happens with proteins during the very first, critical step towards forming larger aggregates.

It turns out that the protein superoxide dismutase interchanges between its normal structure and a misfolded form. During a brief moment the structure becomes partially misfolded to expose sticky patches that normally are hidden in the interior. These patches cause two or several protein molecules to stick together, thereby forming the cornerstone of the larger structures that are believed to underlie ALS.

The research team headed by Mikael Akke at the Center for Molecular Protein Science of Lund University used NMR spectroscopy to create a snapshot of the misfolded structure, which had not previously been seen. Knowledge of the misfolded protein structure potentially makes possible future efforts to rationally design drugs that prevent the misfolding event and hence the development of ALS.

[tdamess]

thank you for information , wouldn't it be wonderful

[GlenBrittle]

OK ... that was interesting.

[halfin]

It's amazing what they can do now with scientific research, and every bit helps. But in this case I am not so sure that this is going to shed that much light on ALS. They have found more information about how the SOD1 mutation that causes some forms of familial ALS can lead to the so-called aggregates of the SOD1 protein, which are thought to be toxic and harmful to the cell. I have seen several researchers proposing that this form of protein aggregation (many protein molecules sticking together) may be a unifying concept behind the diseases mentioned, like Alzheimer's and Parkinson's. I've also seen Huntington's Disease inclued, a bad one that causes early dementia.

It is an attractive theory that all these different diseases may have the same underlying mechanism. But I am not so sure it works for ALS. I don't think it is known whether most cases of sporadic ALS have protein aggregates. There are a lot of things going wrong in a neuron sick with ALS but protein aggregation is not always observed, from what I understand.

I am worried that the elegance of this theory may tempt researchers to pursue a path which will ultimately not be that helpful to the majority of ALS patients. Only 2% of PALS have the SOD1 gene mutation that is known to lead to these SOD1 aggregates being studied here.

100% of ALS mice have SOD1 gene mutations, because that is how they were made. They all have these SOD1 protein aggregates. You can take a healthy strain of mice, introduce the bad SOD1 gene, and they all get ALS. So it does appear that SOD1 aggregates are SUFFICIENT to cause ALS. But that does not mean that SOD1 aggregates or protein aggregates in general are NECESSARY to cause ALS. It could well be that the majority of us with ALS have no significant protein aggregation problem. Focusing too hard on this concept as a "magic bullet" to cure AD, PD, HD and ALS in one fell swoop is so tempting that I fear it is going to draw in research dollars, but I am afraid it won't work, at least not for ALS.

Of course, merely learning how SOD1 aggregation causes ALS in mice and in the 2% of PALS who have it would be a great step forward. Every new discovery is another piece of the puzzle. Plus being able to cure even 2% of PALS would be a miraculous result at this point. But I just hope that researchers don't get too sucked into this protein aggregation theory as the cure-all, at least until they can establish that something like this is going on in sporadic ALS.