Stanford University researchers have recently published an interesting report in which they not only propose a novel biomarker for Parkinson’s, but also provide some compelling data for a novel therapeutic approach.
Their research focuses on a protein called Miro, which is involved in the removal of old or faulty mitochondria. Mitochondria are the power stations of each cells, providing cells with the energy they require to do what they do.
Specifically, the researchers found that Miro refuses to let go of mitochndria in people with Parkinson’s (which could act as a biomarker for the condition). They also found that pharmacologically forcing Miro to let go, resulted in neuroprotective benefits in models of Parkinson’s
In today’s post, we will discuss what Miro is, what the results of the new research suggest, and we will consider what will happen next.
Every now and then a research report comes along and you think: “Whoa, that’s amazing!”
It a piece of work that breaks down your cynicism (which you have proudly built up over years of failed experiments) and disciplined scepticism (a critical ingredient for a career in scientific research – mantra: ‘question everything’). And for a moment you are taken in by the remarkable beauty of not just good research, but biology itself.
A couple of weeks ago, one such research report was published.
This is it here:
Title: Miro1 Marks Parkinson’s Disease Subset and Miro1 Reducer Rescues Neuron Loss in Parkinson’s Models.
Authors: Hsieh CH, Li L, Vanhauwaert R, Nguyen KT, Davis MD, Bu G, Wszolek ZK, Wang X.
Journal: Cell Metab. 2019 Sep 23. [Epub ahead of print]
It’s a really interesting study for several reasons.
So what did they report?
A lot of Parkinson’s research is focused on antioxidants – molecules that can reduce the level of stress a cell is under when it is not feeling well.
One of the most widely discussed antioxidants on Parkinson’s online forums is a molecule called N–acetylcysteine (or NAC).
Recently, the results of a small clinical trial – in which NAC was administered to people with Parkinson’s – have been published. The results are rather interesting.
In today’s post, we will discuss what NAC is, why it is important in the context of Parkinson’s, and we will look at what the new clinical trial report suggests about this molecule.
NAC. Source: Draxe
One question I get asked a lot is “What do you think of NAC?”
And I usually answer with my standard “I’m not a clinician, just an ex-research scientist. I can’t talk about medications or supplements, etc…”
But recently some interesting new data has been published regarding NAC and it’s kind of interesting.
What is NAC?
N-acetylcysteine (or NAC; also known as Acetylcysteine – commercially named Mucomyst) is a prodrug – that is a compound that undergoes a transformation when ingested by the body and then begins exhibiting pharmacological effects.
Acetylcysteine. Source: Wikimedia
Acetylcysteine serves as a prodrug to a protein called L-cysteine, and – just as L-dopa is an intermediate in the production of dopamine – L-cysteine is an intermediate in the production of another protein called glutathione.
If you remember nothing else today, remember this: Acetylcysteine allows for increased production of glutathione.
And what is glutathione?
Today’s post will be something a little different: 12 months ago today I stepped away from being a Parkinson’s research scientist and joined the Cure Parkinson’s Trust in a new role of deputy director of Research.
It has been an amazing (and very busy – note the back dating of this post!) year! I definitely have no regrets, and the honeymoon is certainly not over – I am still very much loving the new role and the challenges/opportunities it brings.
There have been some major adjustments though and a few unexpected surprises.
In today’s post, I will discuss what I have learnt over the last 12 months and share some of my observations.
As regular readers will know, after 15 years of both lab- and clinic-based Parkinson’s research, last year on the 1st October I stepped away from the academic world to take on a new role as the Deputy Director of Research at the Cure Parkinson’s Trust.
It was a rather crazy moment for me personally, because at the same time that I was being offered this deputy director job, I was also being offered a lecturer position at a UK university.
A university lecturer. Source: Salford
Now, understand dear reader that I had been gunning for a lecturer position for the last 5 years – completing dozens of applications and only being invited to a handful of interviews. It had been a long hard slog, but having my own research group had been the goal for a long time. I was so focused on that idea, that I had not really entertained any other options.
So it was somewhat bewildering when a group like the Cure Parkinson’s Trust came out of left field and offered me something completely different.
And it was truly one of the more surreal moments of my life to then actually say ‘Sorry, but no thanks‘ to the one thing that I had been striving for for so long, and to say ‘Yes please!‘ to this fascinating second option.
But the decision to join the Trust was very easy in the end.
What do you mean?
At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during September 2019.
The post is divided into seven parts based on the type of research:
So, what happened during September 2019?
In world news:
11th September – Astronomers announced the detection of water in the atmosphere of an exoplanet called K2-18b – the first such discovery for an exoplanet in the habitable zone around a star (Click here to read more about this).
17th September – Josh Thompson from New Zealand was going to be made redundant, so he hired a clown to take to his redundancy meeting as his ‘support person’ (as is provided by NZ law). Joe the clown made sad faces when the conversation went negative and also made balloon animals throughout the meeting (only in NZ! – Click here to read more about this):
20th September – The Rugby World Cup started in Japan… and we all know who’s going to win (famous last words!)
28th September – SpaceX presented the Mark1 – the first prototype of their ‘Starship’ which is being developed for interplanetary travel.
And it was with sadness that the Parkinson’s research community heard about the passing of Prof Sir Chris Dobson. Most readers will not be aware of his incredible contributions to the field of Parkinson’s and neurodegeneration in general – he will be missed (Click here to read more about this).
In the world of Parkinson’s research, a great deal of new research and news was reported:
In September 2019, there were 831 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (6215 for all of 2019 so far, and compared to 5978 at the same time in 2018). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).
The top 5 pieces of Parkinson’s news
Yesterday the Aligning Science Across Parkinson’s (ASAP) initiative published a point of view in the scientific journal eLife. It laid out the objectives, themes and philosophy of an enormous new scientific effort to better understand Parkinson’s.
The overall project is being led by a Nobel prize winner scientist and employing the considerable resources of a very wealthy family that has been affected by Parkinson’s.
In today’s post we will have a look at what the ASAP initiative is planning to do and how it will hopefully significantly enhance our understanding of Parkinson’s.
Google co-founder Sergey Brin. Source: Emaze
Every so often something comes along that is so ‘next level’ in its scale and ambition that it gives you pause.
Two years ago, key Parkinson’s researchers from around the world were invited to the Milken Institute Center in for a grand meeting that was organised to plan out the foundations of a major new Parkinson’s research program that was to be called Aligning Science Across Parkinson’s (or ASAP).
The event was organised by Google co-founder Sergey Brin and his family foundation. The Brin family have been affected by Parkinson’s (Sergey’s mother and aunt both have the condition, and Sergey has a genetic risk factor that increases his risk of developing Parkinson’s).
The Brin Family – Sergey and his mother on the right. Source: CS
Sergey and his mother both carry a genetic variation in a region of DNA called PARK8. It is also known as Leucine-rich repeat kinase 2 (or simply LRRK2 – pronounced ‘lark 2’). The variant increases the risk of developing an young-onset, slow progressing form of Parkinson’s (Click here to read more about LRRK2). Sergey may never develop the condition, but he has decided not to take any chances. He has taken out an “insurance policy” by investing hundreds of millions of dollars into Parkinson’s research.
Part of that insurance policy is the ASAP effort.
And ASAP is being coordinated by Prof Randy Schekman.
Who is Prof Randy Schekman?
Theories of viral agents as possible causal (or influencing) factors in Parkinson’s have long existed.
This week a research team from Colorado in the USA published a new report demonstrating that mice infected with a mosquito-borne alphavirus (called Western equine encephalitis virus) develop Parkinson’s-like features.
These features include the loss of dopamine neurons, increased neuroinflammation, locomotor issues, and the wide spread presence of aggregated protein (all classical hallmarks of the Parkinsonian brain).
In today’s post, we will look at what mosquito-borne alphaviruses are, what this new study found, and how the results could help us to better understand some cases of Parkinson’s.
Electron micro photograph of Influenza viruses. Source: Neuro-hemin
Between January 1918 and December 1920, there were two terrible outbreaks of an influenza virus.
The event became known as the 1918 flu pandemic.
Approximately 500 million people across the globe were infected by the H1N1 influenza virus during this period, and there were approximately 50 to 100 million associated death.
Now, to put that into perspective for you, that was basically 3-5% of the world’s population at that time.
1918 Spanish flu. Source: Chronicle
At the time, much of the world was blind to these events. Given that this pandemic occurred during World War 1, censors limited the media coverage of the pandemic in many countries in order to try and maintain some sort of morale (very thoughtful of them).
The Spanish media, however, were not censored and this is why the 1918 pandemic is often referred to as the ‘Spanish flu’.
But at the same time that H1N1 influenza virus was causing havoc, a Romanian born neurologist named Constantin von Economo noticed something interesting.
What did he notice?
This week exciting new research from a collaboration between Chinese researchers and scientists at the University of Iowa has pointed towards a clinically-available, generic drug that could be re-purposed for Parkinson’s.
The researchers found a drug called Terazosin – which is used for the treatment of enlarged prostates and high blood pressure – can boost energy production in neurons, and also rescue multiple preclinical models of Parkinson’s (including human cell cultures).
Most intriguing, however, was their discovery that people taking Terazosin (or similar drugs) have a reduced incidence of Parkinson’s, and people with Parkinson’s who take Terazosin seem to have less disease progression.
In today’s post, we will look at what Terazosin is, how it functions, what this new research suggests, and how the finding is being taken forward.
Reader questions. Source: Yoursalesplaybook
So I have had a few inquiries over the last 24 hours.
Lots of questions.
A wee bit of interest in some recent Parkinson’s associated research.
It seems that there was a bit of excitement generated by press releases regarding new research from a group of researchers in China and the University of Iowa suggesting that a commonly used blood pressure and prostate treatment called Terazosin not only had beneficial effects in multiple models of Parkinson’s, but also reduced the incidence of Parkinson’s in people taking the drug.
Terazosin. Source: Wikipedia
Here is the study in question:
Title: Enhancing glycolysis attenuates Parkinson’s disease progression in models and clinical databases.
Authors: Cai R, Zhang Y, Simmering JE, Schultz JL, Li Y, Fernandez-Carasa I, Consiglio A, Raya A, Polgreen PM, Narayanan NS, Yuan Y, Chen Z, Su W, Han Y, Zhao C, Gao L, Ji X, Welsh MJ, Liu L.
Journal: J Clin Invest. 2019 Sep 16. pii: 129987.
PMID: 31524631 (This report is OPEN ACCESS if you would like to read it)
In this study, the researchers investigated the properties of a drug called terazosin in various models of Parkinson’s.
What is terazosin?
The results of a clinical trial published this week not only provide further evidence that exercise has beneficial effects for people with Parkinson’s, but may also be disease modifying.
Researchers in the Netherlands recruited 130 people with Parkinson’s to take part in a study of clinical exercise. The participants were divided into 2 groups – one instructed to do aerobic exercise (an exergaming activity), while the other group was given stretching activities.
After 6 months, the investigators found that the symptoms of the aerobic exercise group had progressed at a slower rate than the other group, suggesting that the benefits of the exercise regime were clinically relevant.
In today’s post, we will review the study, discuss what exergaming is, and explore what may happen next.
A sweet ride. Source: Electricbikereview
I recently bought a bike (not the one above). Why? Because I need to get fit.
Honestly, I am so unfit at the moment. Due to a reconstructed foot, running is not an option. The gym and the pool are too expensive and time consuming (read: I’m cheap and lazy).
So I bought a bike, with the goal of getting out into the country side several times a week. And I have to say: I absolutely love it! The freedom of it has been smiling like an idiot, and reminiscing of a younger age when I was less beautiful.
But all kidding aside, cycling is a great way of keeping fit and there is some REALLY interesting Parkinson’s research being done on cycling at the moment.
What do you mean?
For the last 21 years, the protein alpha synuclein has developed a reputation as public enemy #1 in the world of Parkinson’s.
Tiny errors in the DNA that provides the instructions from making the alpha synuclein protein were found to be the first genetic risk factor for the condition, and then the protein itself was found to be present in Lewy bodies – one of the cardinal features of Parkinson’s in the brain.
In addition, animal models of Parkinson’s involving the production of high levels of alpha synuclein have demonstrated that this build up of protein can be neurotoxic, and it has been reported that alpha synuclein deposits can appear in cells that had been transplanted into the brains of people with the Parkinson’s.
But very recently a new theory (and supporting data) regarding this protein has been proposed, and it paints a slightly different picture.
In today’s post we will look at this new theory (and the provided data), and consider what this could mean for our efforts to therapeutically deal with Parkinson’s.
Ok, today’s post is diving straight into the science lesson.
No preamble, just good old cell biology.
In almost every cell in your body, there is a structure called the nucleus. It is rather critical to life as we know it, because the nucleus is the vault which holds the blue prints (aka DNA) for making and maintaining a copy of ‘you’.
The nucleus of a cell. Source: Biologywise
The nucleus is a very busy area of any cell as it provides the instructions for cellular function. At any point in the day or night, many regions of the DNA are continuously being read and converted in RNA (in a process called transcription).
While DNA is the blue print, RNA is the facsimile of a region of DNA that is used for making a particular protein. While DNA is precious, unique, and must be carefully guarded, the copied version (RNA) is readily disposable. Once produced (or transcribed), each piece of RNA will exit the nucleus and enter an adjoining structure called the endoplasmic reticulum. On a very basic level, the endoplasmic reticulum is where the RNA facsimile of the instructions is used to produce protein.
Making a protein. Source: Quora
Some of these newly formed proteins will be released outside of the cell (to send messages to other cells), while some other newly formed proteins will be transported to distant parts of the cell to do specific tasks. But another collection of the newly formed proteins will be shipped back to the nucleus where they will play important roles in maintaining, transcribing, monitoring, or repairing the precious DNA.
Recently published research suggests that the Parkinson’s associated protein alpha synuclein may have a function in the protection of DNA.
Specifically, it appears to be involved with DNA repair.
Remind me again: What is alpha synuclein?
A major focus on Parkinson’s research is inflammation.
Inflammation is a vital part of our immune system’s response to infection or injury. It is means by which the body signals to the cells of immune system that something might be wrong and help is required. It is a complex, multi-stage process, involving many different mechanisms which help to amplify and resolve the response.
Recently, some researchers reported some interesting data regarding the ‘resolving’ aspect of the inflammatory response in Parkinson’s. It involved a protein called Resolvin.
In today’s post, we will look at what Resolvin is, what the new research reported, and how this information could be useful in the development of future therapies for Parkinson’s.
Spot the unhealthy cell – exhibiting signs of stress (yellow). Source: Gettyimages
When cells in your body are stressed or sick, they begin to release tiny messenger proteins which inform the rest of your body that something is wrong.
When enough of these messenger proteins are released that the immune system becomes activated, it can cause inflammation.
What is inflammation?
Inflammation is a critical part of the immune system’s response to trouble. It is the body’s way of communicating to the immune system that something is wrong and activating it so that it can help deal with the situation.
By releasing the messenger proteins (called cytokines), injured/sick cells kick off a process that results in multiple types of immune cells entering the troubled area of the body and undertaking very specific tasks.
The inflammatory process. Source: Trainingcor
The strength of the immune response depends on the volume of the signal arising from those released messenger proteins. And there are processes that can amplify the immune response.
But an important component of the immune response that is often overlooked is resolution.
Once an infection/injury has been dealt with, the immune response must be resolved. And there are tiny messenger proteins that our body producing naturally which involved in dampening down the immune response. They are typically released when a situation has been resolved.
One group of resolving messenger proteins are called Resolvins.
What are Resolvins?