Blogging with Parkinson's

A personal perspective on Young Onset Parkinson's


Buzz about Vitamin K2

There is a lot of interest in vitamin K2 at the moment; it has been shown to reverse the symptomatic effects of one of the genetic defects that causes Parkinson’s. In fruit flies.

It’s a long way from fruit flies to human beings, but, as it happens, these popular research insects share the PINK1 gene with us humans, and defects in the fruit fly version have a similar effect on the insects as they do on people. Continue reading



Coffee and Genes

"Coffee for Two", oil on paper

I like coffee, but I don’t consume large amounts of it (as may be evident from the cleanliness of my coffee-making paraphernalia in the painting).

But some people who do drink lots and lots and lots of coffee may be doing themselves a favour – as well as keeping themselves awake, of course.  It’s actually pretty old news that caffeine has, in large quantities, a protective effect against developing Parkinson’s. The new news is that the effectiveness of this extreme coffee consumption may be genetic. Apparently, heavy coffee drinkers with a particular variant of the GRIN2A gene (“which regulates brain signals that control movement and behavior”) are even less likely to develop Parkinson’s than other heavy coffee drinkers Continue reading


How PINK1 mutations cause Parkinson’s

If we know what causes Parkinson’s, and how, we can understand it better. If we understand it better, we might be able to prevent it, or treat it, or stop it in its tracks, or even roll it back as if it never ever happened (the last seems unlikely). But understanding is key.

And that’s what this science story is about. Researchers in Dundee have used an insect version of the gene PINK1, known to be one of the genes whose mutation can cause Parkinson’s, to work out how the mutation causes Parkinson’s. A summary of the research is given in a Royal Society news article.

And even better, they’ve published it in the Royal Society’s new open format – which means, dear reader, that you, too, can plough through impenetrable scientific jargon in the hope of extracting some… er, hope. Actually, it isn’t that bad. There’s quite a bit of plain prose that tells you pretty much everything you might want to know. Even so, I have endeavoured to select the key elements for your delight and delectation.

Mutations in the protein kinase PINK1 (PTEN-induced kinase 1) gene cause hereditary Parkinson’s disease. Patients harbouring PINK1 mutations typically present with early-onset Parkinson’s disease, with a mean age of onset in their 30s.

Extract from the Introduction to “Discovery of catalytically active orthologues of the Parkinson’s disease kinase PINK1: analysis of substrate specificity and impact of mutations “ by Helen I. Woodroof, Joe H. Pogson, Mike Begley, Lewis C. Cantley, Maria Deak,David G. Campbell, Daan M. F. van Aalten, Alexander J. Whitworth, Dario R. Alessi1 and Miratul M. K. Muqit, published in Open Biology, November 2011.

… which is quite young. So we’re talking definite young onset here; I suppose it’s possible that I could have a PINK1 mutation. So what does PINK1 do?

The function of PINK1 remains poorly understood, although, in mammalian cells, several studies suggest that PINK1 controls another Parkinson’s disease-associated enzyme, namely the parkin E3 ligase, by recruiting it to the mitochondrial membrane through an as-yet-undefined mechanism.

Extract from the Introduction, ibid.

They’re not sure. However, it has been determined that knocking out PINK1 in mice has no observable effect – but in fruit flies, the lack of a functional PINK1 causes Parkinsonian symptoms, “including motor deficits, neuronal loss and mitochondrial abnormalities.”

It turns out that the insect PINK1 is easier to work with in the lab than the human variant. The researchers were able to establish that “most Parkinson’s disease-associated missense mutations ablate or markedly inhibit PINK1 kinase activity.” I think this means that mutations in the PINK1 gene that cause Parkinson’s are likely to be related to the kinase activity of PINK1.

Which begs the question, “What is a kinase?” In answer, Wikipedia says that a kinase is “a type of enzyme that transfers phosphate groups from high-energy donor molecules […] to specific substrates.”

The article goes on to describe the experimental process and its results.

We determined the effects of Parkinson’s disease-associated mutations on PINK1 catalytic activity by selecting 14 […] mutations that lead to early-onset Parkinson’s disease […]. All bar one of the selected mutations are located within the kinase domain […].


Our results suggest that missense PINK1 mutations situated within the kinase domain exert their Parkinson’s disease-causing effects by markedly suppressing kinase activity […]. This emphasizes the importance of identifying the key physiological substrates of PINK1 in order to understand how the loss of kinase activity leads to neurodegeneration in Parkinson’s disease.

Extract from the Results section, ibid.

After a short discussion of the kinase inhibition treatments that are currently being developed for other diseases and the possibility of such treatments inducing Parkinson’s (the risk is judged to be low),  they offer their conculsions:

In conclusion, we report for the first time a novel method to express an active form of PINK1. This has enabled us to develop an assay to quantitatively assess PINK1 activity and investigate its substrate specificity. Our work suggests that, with the exception of the C125G mutation [which lies outside of the kinase domain], all other Parkinson’s disease mutations assessed are likely to exert their disease-causing effects by suppressing kinase catalytic activity. These observations emphasize the importance of PINK1 kinase activity in preventing the onset of Parkinson’s disease, and that the key challenge in future will be to identify PINK1 substrates and study the relevance of these in Parkinson’s disease. We hope that the results presented in this study will aid with assaying PINK1 catalytic activity and in the hunt for substrates of this enzyme.

Extract from the Results section, ibid.

This study may not present any solutions to the problem of Parkinson’s, but it does contain a new piece of the jigsaw that will help the scientific community understand the disease and, hopefully, create new and effective treatments in the future.

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23andMe make some Progress

A bad pun.

23andMe, the private genetic company with a special interest in Parkinson’s, has discovered a gene that may protect against Parkinson’s.

The LRRK2 gene is recognized as a significant risk factor for Parkinson’s disease. Of the approximately 1 in 10,000 people who carry a mutation called G2019S on the LRRK2 gene, about half develop Parkinson’s disease. 23andMe has a large cohort of individuals who carry the G2019S mutation but surprisingly, do not have Parkinson’s. In examining this cohort, 23andMe discovered the potentially protective nature of SGK1.

23andMe – Press Release

The Scripps Research Institute will investigate the finding further, with the aim of trying to “identify a new and potentially vital therapeutic target for Parkinson’s disease”, with funding from the Michael J. Fox Foundation.

Unfortunately, it doesn’t seem to be possible to extract specific gene data from the 23andMe Web interface; I was curious as to whether I had the G2019S mutation in LRRK2, but wasn’t able to find out.