Alpha synuclein is a protein that is closely associated with Parkinson’s. But exactly if and how it is connected to the neurodegenerative process underlying the condition, remains unclear.
Last week researchers reported that removing a particular form of alpha synuclein in mice results in a very early onset appearance of characteristics that closely resemble the features of Parkinson’s that we observe in humans. This finding has caused some excitement in the research community, as not only does this tell us more about the alpha synuclein protein, but it may also provide us with a useful, more disease-relevant mouse model for testing therapies.
In today’s post, we will discuss what alpha synuclein is, explain which form of the protein was disrupted in this mouse model, review the results of the new study, and look at how tetramer stablising drugs could be a new area of PD therapeutics.
The 337 metre (1,106 ft) long USS Gerald R. Ford. Source: Wikipedia
Imagine you and I are standing in front of the world’s largest aircraft carrier, the USS Gerald R. Ford.
It is a VAST warship – measuring in at 337 metres (1,106 ft) in length, 76 metres (250 feet) in height – and it is a wonder of engineering composed of over a billion individual components.
And as we are standing there, gazing up at this amazing machine, I turn to you and put a nut & bolt into the palm of your hand.
A nut and bolt. Source: Atechleader
You look down at it for a moment, then turn to me, puzzled.
And that is when I say: “I would like you to find (without aid/instructions) where on this ship versions of this particular type of nut and bolt live, and try to determine exactly what functions they have“.
Where would you even start?
What tools would you use for the job? Considering the size and complexity of the vessel, would you simply give up before even starting?
It sounds like a ridiculously daunting task, but this is in effect what neurobiologists are trying to do with their study of the brain. They start with a protein – one of the functional pieces of machinery inside each cell of our body – and then try to determine where in the brain it lives (the easy part) and what it does exactly (the REALLY hard part – most proteins have multiple functions and different configurations).
A good example of this is the Parkinson’s-associated protein alpha synuclein:
Alpha synuclein. Source: Wikipedia
Alpha synuclein is one of the most abundant proteins in our brains – making up about 1% of all the proteins floating around in each neuron in your head – and it is a very well studied protein (with over 9700 research reports listed on the Pubmed search engine with the key words ‘alpha synuclein’).
But here’s the thing: we are not entirely clear on what alpha synuclein actually does inside the cell.
In fact, biologists are not even sure about what the ‘native’ form of alpha synuclein is!
What do you mean?