Forget Special K, maybe focus on LysoK

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Over the last 20 years, researchers have identified a number of genetic variations that can confer an increased risk of developing Parkinson’s. Tiny alterations in regions of DNA (called genes) – which provide the instructions for making a protein – can increase one’s chances of Parkinson’s.

A better understanding of the biological pathways associated with these genetic risk factors is opening up vast new areas of research.

Recently researchers have been exploring the biology behind one particular genetic risk factor – involving a gene called TMEM175 – and they have discovered something quite unexpected: While one genetic variation in the TMEM175 gene increases the risk of Parkinson’s, another variation reduces it.

In today’s post, we will explore the biology of TMEM175, review what the results of the new research indicate, and consider why these findings might be interesting in terms of potential future therapeutic targets.

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Wadlow (back left). Source: Telegraph

Robert Pershing Wadlow was always in the back of school photos.

Born February 22nd 1918, Wadlow’s birth certificate indicated that he was “normal height and weight“, but from that point onwards, there was nothing normal about his rate of growth.

By the time, Robert was 8 years old, he was taller than his father (he was 6 foot/183cm). And eight years later when he turned 16, Robert was 8 foot 1 (2.47 m)… and he was still growing.

Here is a picture of him with his family at 19 years of age:

Source: Businessinsider

Robert was the tallest person in recorded history, and at the time of his death – at the tragically young age of 22 – Robert was almost 9 feet tall (8 ft 11; 2.72 m)… and still growing.

His incredible growth was caused by a condition called hyperplasia of his pituitary gland. This condition that results in an overactive pituitary gland which causes an abnormally high level of the human growth hormone to be produced.

Source: Britannica

Human growth hormone (or somatotropin) is a peptide hormone that belongs to a much larger group of molecules that are referred to as growth factors.

In general terms, growth factors are small molecule that plays an important and fundamental role in biology. They stimulate cell proliferation, wound healing, and occasionally cellular differentiation.

And Robert’s story is an example of how powerful the effect these tiny molecules can have.

Growth factors are secreted from one cell and they float around in the extracellular world until they interact with another cell and initiate survival- and growth-related processes.

Source: Wikimedia

We have often discussed growth factors on this website in the past, with posts of growth factors like GDNF (Click here to read a SoPD about this) and CDNF (Click here to read a SoPD post on this). These discussions have largely focused on how growth factors could have neuroprotective and regenerative potential for Parkinson’s, stimulating survival and growth of cells.

Recently, however, new research has been published that demonstrates how some of these growth factors could be influencing an entirely different aspect of cellular biology that is connected to Parkinson’s: lysosomal function.

What is lysosomal function?

Continue reading “Forget Special K, maybe focus on LysoK”

On the importance of Calcium

Recently researcher from the University of Cambridge reported that an imbalance in calcium and the Parkinson’s-associated protein alpha synuclein can cause the clustering of synaptic vesicles.

What does this mean? And should we reduce our calcium intake as a result?

In today’s post, we will review the research report, consider the biology behind the findings and how it could relate to Parkinson’s, and discuss what can or should be done.


Me and Brie. Source: Wikipedia

When I turned 25, I realised that my body no longer accepted cheese.

This was a very serious problem.

You see, I still really liked cheese.

A bottle of red wine, a baguette and a chunk of brie – is there any better combination in life?

So obviously my body and I had a falling out. And yes, it got ugly. I wanted things to keep going the way they had always been, so I tried to make things interesting with new and exotic kinds of cheeses, which my body didn’t want to know about it. It rejected all of my efforts. And after a while, I gradually started resenting my body for not letting me be who I was.

We sought help. We tried interventions. But sadly, nothing worked.

And then things got really bad: My body decided that it didn’t have room in its life for yogurt, milk or even ice cream anymore (not even ice cream!!!). Basically no dairy what so ever.

There’s something’s missing in my life. Source: Morellisices

OMG. How did you survive without ice cream?

Well, I’ll tell ye – it’s been rough.

All silliness aside though, here is what I know: It is actually very common to develop a lactase deficiency as we get older – lactase being the enzyme responsible for the digestion of whole milk. In fact, about 65% of the global population has a reduced ability to digest lactose after infancy (Source: NIH). I am not lactose intolerant (one of the few tests that I actually aced in my life), but I do have trouble digesting a particular component of dairy products – which can result in discomfort and socially embarrassing situations (one day over a drink I’ll tell you the ‘cheese fondue story’). Curiously, that mystery ingredient is also present in products that have no dairy (such as mayonnaise – it absolutely kills me).

But spare me your tears, if one is forced to drop a particular food group, dairy is not too bad (if I am ever forced to give up wine, I swear I’ll go postal).

My biggest concern when I dropped dairy, however, was “where was I going to get my daily requirements of calcium?“.

Understand that calcium is really rather important.

Why is calcium important?

Continue reading “On the importance of Calcium”

O’mice an’ men – gang aft agley

This week a group of scientists have published an article which indicates differences between mice and human beings, calling into question the use of these mice in Parkinson’s disease research.

The results could explain way mice do not get Parkinson’s disease, and they may also partly explain why humans do.

In today’s post we will outline the new research, discuss the results, and look at whether Levodopa treatment may (or may not) be a problem.


The humble lab mouse. Source: PBS

Much of our understanding of modern biology is derived from the “lower organisms”.

From yeast to snails (there is a post coming shortly on a snail model of Parkinson’s disease – I kid you not) and from flies to mice, a great deal of what we know about basic biology comes from experimentation on these creatures. So much in fact that many of our current ideas about neurodegenerative diseases result from modelling those conditions in these creatures.

Now say what you like about the ethics and morality of this approach, these organisms have been useful until now. And I say ‘until now’ because an interesting research report was released this week which may call into question much of the knowledge we have from the modelling of Parkinson’s disease is these creatures.

You see, here’s the thing: Flies don’t naturally develop Parkinson’s disease.

Nor do mice. Or snails.

Or yeast for that matter.

So we are forcing a very un-natural state upon the biology of these creatures and then studying the response/effect. Which could be giving us strange results that don’t necessarily apply to human beings. And this may explain our long history of failed clinical trials.

We work with the best tools we have, but it those tools are flawed…

What did the new research report find?

This is the study:


Title: Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease
Authors: Burbulla LF, Song P, Mazzulli JR, Zampese E, Wong YC, Jeon S, Santos DP, Blanz J, Obermaier CD, Strojny C, Savas JN, Kiskinis E, Zhuang X, Krüger R, Surmeier DJ, Krainc D
Journal: Science, 07 Sept 2017 – Early online publication
PMID: 28882997

The researchers who conducted this study began by growing dopamine neurons – a type of cell badly affected by Parkinson’s disease – from induced pluripotent stem (IPS) cells.

What are induced pluripotent stem cells?

Continue reading “O’mice an’ men – gang aft agley”