As proteínas são os blocos de construção e máquinas que fazem e correm em nossos corpos. Neste artigo, examinamos mais de perto 2 proteínas, alfa-sinucleína e tau, que podem estar no coração do Parkinson.
A tale of two proteins
Proteins are the building blocks and machines that make and run our bodies. In this article, we take a closer look at 2 proteins, alpha-synuclein and tau, that may lie at the heart of Parkinson’s.
What is a protein?
There are thousands of different types of proteins in our bodies. They come in lots of shapes and sizes and are responsible for growth, development and millions of tasks that keep us healthy.
Here are a few examples:
Enzymes are proteins that aid chemical reactions, for example digestive enzymes in the stomach help to break down proteins in food.
Antibodies are proteins produced by the immune system that identify and remove foreign invaders to prevent infection.
Proteins like collagen and elastin provide structural support to tissues such as bone and skin.
Hormones are proteins that help regulate our bodies, for instance insulin helps control blood sugar levels, and estrogen helps regulate the development of the female reproductive system.
When proteins go rogue
To do their jobs properly inside cells, proteins must first fold themselves into the correct shape.
If they don’t, trouble can result and problems with misbehaving proteins are thought to be central to the loss of cells in neurodegenerative conditions, like Parkinson’s and Alzheimer’s.
In both conditions proteins that are the wrong shape or ‘misfolded’ build up and stick together, forming clumps of proteins inside the affected brain cells.
In Parkinson’s, the main culprit seems to be a protein called alpha-synuclein which misfolds and forms sticky clumps called Lewy bodies.
Lewy bodies show in brown
Despite decades of research we still have an incomplete understanding of this mysterious protein. When it’s healthy and working properly, we believe it may play a role in helping brain cells to send messages to other brain cells — but it may be involved in several other activities too.
We don’t completely understand why alpha-synuclein becomes misfolded in Parkinson’s and how this causes problems inside cells.
Crucially though, research has suggested that alpha-synuclein may be important in the spread of problems from cell to cell inside the brain. Researchers have shown that toxic, misfolded alpha-synuclein can escape from brain cells and be taken in to neighbouring cells, which then go on to develop problems.
As a result, research teams are now working to develop new treatments that could halt the spread of alpha-synuclein in the brain — including innovative approaches such as vaccines.
Tau — a new protein on the block
Alpha-synuclein has hogged the limelight in Parkinson’s research for decades but interest is now building around another protein called tau.
If you’ve heard of the ‘tau’ protein before, it’s probably in the context of Alzheimer’s rather than Parkinson’s. Other tau-related conditions include progressive supranuclear palsy (PSP), which is often misdiagnosed as Parkinson’s, and corticobasal degeneration (CBD).
Tau is a protein which has a really vital role inside our brain cells. It helps to stabilise and maintain the structures that allow different materials to be transported to where they are needed. Because brain cells tend to be quite large and complex, it’s really important that they are able to move things around effectively to keep them healthy and working properly.
This video from the Alzheimer’s Society provides a good introduction to tau
In Alzheimer’s, tau becomes misshapen. This means it can’t do it’s job properly, and the transport network inside brain cells breaks down.
The misshapen tau proteins also get tangled up and form clumps— called neurofibrillary tangles (NFTs) — which can be seen inside the cells affected by Alzheimer’s when you study brain tissue under a microscope.
What’s tau got to do with Parkinson’s?
We don’t tend to see the same tau tangles inside brain cells that are affected by Parkinson’s. But in 2009, large-scale genetic studies provided powerful evidence that tau may play a significant role in Parkinson’s when they showed that variation in the gene that codes for the tau affects the risk of developing the condition.
But if tau doesn’t get tangled up in Parkinson’s, what is it doing?
“Normally functioning tau resides inside our cells and doesn’t do us any harm. But we think that something may trigger a conversion from this harmless version of tau into a toxic version — and that’s when the trouble begins.
“The classic tangles that form in Alzheimer’s and other tau-related conditions like PSP are probably not the primary culprits, it’s the toxic, sticky version of the protein that we now believe does the damage.” Dr Rohan de Silva
Targeting tau to develop new treatments
Rohan received a grant from Parkinson’s UK to study tau in Parkinson’s in 2013.
“Genetic studies have shown that people who have the H1 form of the tau gene are more likely to get Parkinson’s than people with the H2 form. Our work suggests that people with the H1 form of the gene produce more tau protein than people with H2. We also see the same type of spread from cell to cell with tau that we see with alpha-synuclein, so therapies that can reduce the production of tau protein may be helpful.
“During our experiments we discovered something unexpected: a non-coding RNA linked to tau.
“Non-coding RNAs are sections of DNA that do not make proteins but help to regulate the production of proteins. The one that we found helps to fine-tune the production of tau inside brain cells.
“Basically, if you can boost the levels of this non-coding RNA, you can reduce the production of tau protein — and we think simply reducing tau levels inside cells may be beneficial in neurodegenerative conditions.
“As a result of this discovery we have now gained further funding to develop and test whether we can deliver this non-coding RNA using gene therapy to reduce tau levels in mice.
“If we’re successful, we hope to take this approach forward to be developed as a new therapy that can one day be tested in people.”
Tau treatments already in clinical trials
As well as Rohan’s work to develop a therapy that can reduce the production of tau, several major drug companies are pursuing new treatments that aim to mop up excess tau — some of which are already being tested in people in clinical trials. Read more about this here.
While many of these emerging therapies have been developed with Alzheimer’s in mind, the growing understanding of tau’s potential role in Parkinson’s means that they could provide a useful treatment for both conditions. Fonte: Medium.
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