Cutting the supply line: a new anti-cancer strategy?

Image Source: Serial/Trash

After centuries of endeavour, scientists and doctors have made great strides towards improving cancer treatment. Nonetheless, while conventional therapy has undoubtedly saved innumerable lives, a worrying number of tumours remain inoperable and incurable by chemo- or radiotherapy. Thus, the search for more refined anti-cancer drugs continues, and paving the way is a research team led by Dr Janine Erler, whose recent discoveries raise hopes of a new therapeutic strategy.

What is wrong with current cancer treatment?

There are two principal barriers to effective treatment: firstly, rather than constituting a single disease, cancer actually comprises thousands, each with its own unique aberrations; secondly, cancer occurs when our own cells go awry, making it notoriously difficult to target. Current cancer therapy is like trying to hit a bull’s-eye with a machine gun; even when you hit the target, there is substantial collateral damage, and too often, part of the bull’s-eye remains intact. The goal of cancer research, therefore, is to identify unique aspects of the tumour environment, and develop a ‘silver bullet’ drug to target the tumour more precisely. Accordingly, scientists aim to identify specific ‘weak spots’ in cancerous tumours.

What weak spots have been discovered?

As fast-growing bodies, tumours rely on a large blood supply. To meet this demand, they hijack the body’s own supply line by releasing chemicals that force nearby blood vessels to sprout new offshoots. The main chemical involved is VEGF, and several VEGF-blockers have been developed. Clinical trials of these drugs have been disappointing, however, and there are concerns that blocking all VEGF produced in the body may actually be detrimental in situations where vessel sprouting is essential, such as in wound healing or stroke recovery. To overcome this barrier, Dr Erler’s team have been investigating ways in which we can specifically block VEGF produced by tumours, without interfering in normal and essential vessel growth.

What have Dr Erler’s team found?

In 2011, the group discovered that tumours produce a chemical called LOX, essential for their growth and ability to invade other organs. Because a large blood supply is crucial for tumour growth, they wanted to investigate whether LOX was involved in generating new vessels. In a more recent study, they used cancerous cells genetically engineered to produce either very large or very low quantities of LOX, which they implanted into mice and left to form tumours. Upon dissection, the team noticed that tumours formed from cells with high levels of LOX contained many more new blood vessels than those containing low levels of LOX. 

How does LOX cause blood vessel sprouting?

To address this question, the researchers grew the genetically engineered high-LOX and low-LOX cancer cells in flasks. They then removed the liquid in which they were grown, containing all the chemicals released by the cells, and applied it to isolated blood vessel cells. The vessel cells exposed to high-LOX liquid became much more mobile, and spontaneously formed tubes similar to blood vessels. This suggests that the cells grown in high-LOX conditions receive a ‘sprouting signal’ from their environment that is not present in low-LOX conditions.

Because VEGF is key to new vessel formation, the team suspected that LOX may generate high levels of VEGF, which could then act as the ‘sprouting signal’ for vessel cells. Indeed, when they analysed the liquid removed from high-LOX cancer cells, they found it contained very high levels of VEGF, unlike liquid from low-LOX cells. When the high-LOX cells were treated with a LOX-blocking drug, moreover, the levels of VEGF released dropped dramatically.

VEGF. Image Source: Shutterstock. Copyright: molekuul.be

Is this relevant in humans?

To ascertain whether the relationship between LOX and tumour blood supply is also relevant in humans, the researchers obtained colon samples from colorectal cancer patients and healthy volunteers. They found that the cancerous samples contained much higher levels of LOX and VEGF than healthy colons. Interestingly, the levels of both LOX and VEGF were directly proportional to the number of blood vessels present, and importantly, to the severity of the cancer. Most excitingly, they observed an identical pattern in breast cancer samples, suggesting that LOX may be important in many different types of tumour.

What does this mean for new cancer treatments?

Based on Dr Erler’s research, it is clear that LOX-blocking drugs could theoretically stop the growth and spread of several different types of cancer. That they are capable of eliminating tumours seems unlikely. Nonetheless, a significant benefit of such drugs is their potential use as intervention-sparing agents. Restricting tumour size and spread would undoubtedly facilitate surgical removal, and could reduce the need for chemo- and radiotherapy – notorious for their toxic side effects. While anti-LOX drugs may not be a ‘silver bullet’ cure exactly, they could well refine current treatment strategies, and improve the quality of life of millions of cancer sufferers worldwide.

This summary by Claire Sand was shortlisted for Access to Understanding 2014 and was commended by the judges. It describes research published in the following article, selected for inclusion in the competition by Breakthrough Breast Cancer:

Lysyl oxidase plays a critical role in endothelial cell stimulation to drive tumor angiogenesis

PMCID: PMC3548904

A.M. Baker, D. Bird, J.C. Welti, M. Gourlaouen, G. Lang, G.I. Murray, A.R. Reynolds, T.R. Cox & J.T. Erler. 

Cancer Research (2013) 73(2), 583-594.

Access to Understanding entrants are asked to write a plain English summary of a research article. For Access to Understanding 2014 there were 10 articles to choose from, selected by the Europe PMC funders. The articles are all available from Europe PMC, are free to read and download, and were supported by one or more of the Europe PMC funders.

Look out here and on Twitter @EuropePMC_news for further competition news and other Europe PMC announcements.   

Out of my comfort zone

By Claire Sand, PhD student at King's College London

Note: Claire Sand was highly commended for her entry this year. She was a joint second-place winner in Access to Understanding 2013 competition. Check back tomorrow to read her entry.

After my fantastic experience at Access to Understanding 2013, I was very keen to be involved again this year. My first entry had inspired me to think about pursuing science writing as a potential career path, and since such a job would require me to write about a wide range of subjects, I was keen to test my ability to write about a topic of which I had no prior experience – namely cancer. This allowed me to learn something about a field entirely different from my own area of research (cardiovascular science), and I really enjoyed the challenge of trying to understand a new subject well enough to be able to explain it clearly to other non-experts.  

Access to Understanding 2013: Claire Sand won joint 2nd prize. Pictured here with BHF representative Henry French.

I picked the Cancer Research paper for two reasons: firstly, because I saw it had come from the Institute of Cancer Research in London. As a naïve and slightly misguided undergraduate, I had actually applied for a PhD at the ICR in 2010 (despite having taken no modules in cancer biology), because I was sure it would be an interesting disease to investigate. My ignorance on the subject became embarrassingly apparent at my interview session, and I was not offered the post (a rejection for which I have always been grateful, as I have since discovered that cardiovascular science is my true passion). I had been deeply impressed by this very serious and prestigious institution, however, so I was curious to see what kind of research they were pursuing.

The second reason that I was drawn to this paper was that I could immediately appreciate its clinical significance. As someone who struggled to choose between medicine and science careers, I have always been inspired by research with a strong disease focus, and the relevance of this study to human pathology was very evident. I know from my own field that a considerable proportion of studies carried out in animals later turn out to have limited application in humans, so I was excited to see that the scientists’ findings in lab mice were recapitulated in human samples.

As I have never really followed the cancer literature, I had to spend some time reading around the subject, in order to understand how this research built on current concepts of cancer therapy; particularly how it might help to overcome the disadvantages of using indiscriminate VEGF-blocking drugs. The substantial achievement of these scientists was impressed upon me, the more I read, and I was left feeling hopeful that these studies could truly lead to meaningful advances for cancer sufferers. I was also encouraged to find that I was able to obtain a basic understanding of a field previously unfamiliar to me, and an appreciation of the significance of a piece of research, without excessive time commitments. The publication of lay abstracts and clinical impact assessments with each new research paper, however, would undoubtedly facilitate faster dissemination of new findings to a wider audience (and help scientists keep abreast of progress in areas outside their expertise!).

I was delighted to be short-listed again this year, and really enjoyed the awards ceremony, which was very well run, with enormously interesting guest speakers. I was fortunate to be able to meet one of the authors of my chosen research paper; we had a fascinating conversation, in which he updated me on the progress of his research. I was especially pleased to have been selected once I read the contributions of the other short-listed candidates; the standard of writing this year was exceptionally high, with some truly brilliant phraseology. The winning entry, in particular, stood out immediately, and as a lay reader in the field of neuroscience, I found it immensely gratifying to read such a fluid and lucid description of a physiological process I had previously never had occasion to question.

Access to Understanding 2014: Claire Sand pictured looking through competition booklet before the ceremony.

I will definitely continue to participate in Access to Understanding, not only because I find it personally rewarding, but also because I think the remit of the competition – to increase public awareness of science, by encouraging scientists to share their work – is enormously important for the future of scientific research and medical advancement. In this endeavour, I believe Europe PMC has already been successful: the fact that there were thousands of votes for the People’s Choice Award suggests that there is an appetite for information amongst the public, and that people are curious about these studies that for centuries have been carried out behind the closed doors of limited access and impenetrable jargon. Public engagement ventures are opening those doors, and can only serve to improve the quality of our research efforts, by making scientists more accountable, and by inspiring people to become involved in or donate funds to worthwhile and potentially life-changing research. 

Populations within populations: drug resistance and malaria control

Image design: Serial/Trash

Malaria claims a million lives a year, a majority of which are children, and threatens the lives of billions more within its tropical ranges. It is caused by Plasmodium, a parasite that uses mosquitoes as a way of getting in to and out of humans. Initial infection from the bite of a carrier mosquito is followed by the parasite’s massive proliferation and colonisation of the host’s blood, causing a suite of debilitating symptoms and providing a parasitized food source for the next mosquito. In the absence of a vaccine, prevention and treatment remain our only effective weapons against malaria. Today, the most effective treatment regime relies heavily on artemisinin, a compound from an Asian herb that effectively targets the parasite within red blood cells. But, as was the case for previous anti-malarial drugs, the spectre of artemisinin-resistant Plasmodium strains is rising. Worryingly, as there is currently no clear fall back to artemisinin, a global spread of resistance will seriously harm our ability to tackle the disease.

The research of Miotto, et al. was stimulated by the observation that resistance to artemisinin, and indeed some of its forebear drugs, appears to originate in the same part of the world: the remote mountains of western Cambodia. To tackle the question of why drug resistance originates here, the researchers sought clues within the parasite’s genome. They had previously developed a technique to isolate Plasmodium DNA directly from the blood of infected patients: a blood sample is taken, white blood cells removed (this removes a lot of the human DNA content which can complicate analysis), and DNA extracted and sequenced using modern sequencing technology. For this work they do not require the parasite genome sequenced in its entirety; rather, they seek sufficient coverage to allow reliable identification of variability between samples.

The researchers collected samples from infected patients in west Africa and southeast Asia, including four sites in Cambodia, one in the east and three in the west. A global survey of the genetic data revealed that the Asian and African populations have distinct patterns of genetic variation, consistent with their geographical isolation. Within the Asian sample, the story was a little more complex. Samples from western Cambodia were notably distinct from those in eastern Cambodia and Thailand. The western Cambodian populations were also ‘structured’, that is, the population was split into subpopulations, each with their own distinct genetic signatures. The subpopulations were also relatively inbred, lacking in genetic diversity, which is often a signature of a recent expansion from a small, homogenous population. Crucially, the researchers were able to show that the subpopulations that predominate in western Cambodia showed artemisinin resistance, as infected patients responded poorly to treatment. Thus, while the distinct subpopulations of Plasmodium in western Cambodia are genetically distinct, they present the same problem: artemisinin resistance.

Image Source: Shutterstock Copyright: GuoZhongHua

The beauty of these kinds of genomic studies is that as well as just looking at the variation between groups accross the genome, on a global scale, we can zoom in and focus on the individually varying regions to ask whether these parts do anything relevant. The researchers made the important observation that the western Cambodian subpopulations harbour a number of genetic changes associated with drug resistance, including alterations to genes which control the entrance of molecules into the cell. One of the subpopulations even harboured mutations in genes involved in preventing mutations, raising the intriguing possibility that a general increase in mutability of the genome may provide more drug resistance mutations.

Identifying the source of emerging drug resistance, both in terms of geography and underlying genetic causation, is a critical task if we are to control its spread. Hence the importance of this work for malaria control. The fact that there are multiple, independent artemisinin-resistant subpopulations shows that there are many routes for a parasite to become resistant. In practical terms the genetic signatures within the resistant strains can be used as biomarkers for artemisinin resistance in any sample of Plasmodium DNA, allowing health authorities to monitor its spread. Furthermore these genetic signatures will add to our biological understanding of how the parasites evolve to resist the drug.

We are still however left with our opening question: why Cambodia, specifically why Western Cambodia? The authors propose a number of potential contributory factors, including the potential higher mutation rate, heavy use of drugs and local isolation of the populations (favouring inbreeding) due to the remoteness of the region. General features of host-parasite interactions are thus married with particularities of the region to provide a potent reservoir of drug resistance. Whatever the underlying causes, the next imminent step will be containment of these variants to prevent their global spread.

This summary by Aidan Maartens was shortlisted for Access to Understanding 2014 and was awarded third prize. It describes research published in the following article, selected for inclusion in the competition by the Wellcome Trust:

Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia

PMCID: PMC23624527

O. Miotto, J. Almagro-Garcia, M. Manske, B. MacInnis, S. Campino, K. A. Rockett, ... D. P. Kwiatkowski.

Nature Genetics (2013) 45(6), 648-655.

Access to Understanding entrants are asked to write a plain English summary of a research article. For Access to Understanding 2014 there were 10 articles to choose from, selected by the Europe PMC funders. The articles are all available from Europe PMC, are free to read and download, and were supported by one or more of the Europe PMC funders.

Look out here and on Twitter @EuropePMC_news for further competition news and other Europe PMC announcements.   

A night at the Oscars

By Aidan Maartens, Post-doc student at the Gurdon Institute 

Note: Aidan was awarded third place in this year's Access to Understanding competition. Check back tomorrow to read his winning entry! Congratulations Aidan!

It ended in a pub with a group of us - some entrants, some science-communications people, and one of the judges of the competition - struggling to hear each other over the pub quiz in the background. It had started a couple of hours beforehand, in a reception hall slowly filling up with guests and a rising swell of echoing conversations. We were ushered in to the lecture hall, and a few talks later the awards were announced, photos taken, hands shaken, and conversations had with a bunch of nice people who were in some way linked to the competition. Someone jokingly described it as the science writing Oscars; the pub trip was, then, the glamorous after-party.

Aidan after receiving his award from Sir Mark Walport. 

My motivations to enter Access to Understanding are probably common to most of the applicants: we get some sort of pleasure from writing, and like the chance to get out of the bubble of day to day research while still doing something connected to science. The articles on offer were in a way typical scientific papers, not the blockbuster, creating-synthetic-life or finding-the-Higgs-boson type papers. This is not to denigrate them at all, rather to say that they were more representative of the incremental nature of much scientific progress. The upshot was that writing a summary was a little more challenging, as the message and impact of the work was a bit more nuanced.

I would recommend this sort of competition to other scientists for a number of reasons. Even if you don’t particularly like writing, it’s a good skill to practice. You might even get to learn something new - for me, how next generation sequencing was revolutionizing the way scientists understand drug resistance in malaria. Finally, it lets you, for a few hours at least, get away from your own project and use another part of your brain. Perhaps you’ll get a new perspective on your project when you get back to it.

Beat box: How the brain processes rhythm

Image Source: Serial/Trash

People have little trouble recognising and following the beat in a piece of music. We can even continue to play the beat in our minds once a song has finished. However, despite the ease with which we carry out such a task, the brain activity which underpins it remains a topic of investigation.

Finding the beat – why does it matter?

We’re all familiar with the niggling irritation of a song that’s stuck in our heads. However, few of us are aware that our knack for holding a beat in our thoughts actually makes life easier. The capacity to identify patterns in streams of sound supports many forms of human behaviour, including moving, speaking and listening. 

If the ability to generate this internal rhythm is disrupted, such as in Parkinson’s disease, problems begin to arise. People with Parkinson’s disease have difficulty with psychological tasks, such as holding a beat in their minds, as well as with practical tasks, such as walking. The more we know about the regions of the brain that are causing these difficulties, the more effective we will be in designing treatments to combat them. Previous research suggests that a set of brain structures known as the basal ganglia are involved in identifying and following a beat.

What are the basal ganglia?

The basal ganglia are a network of brain regions that are involved in movement and action. Many of the regions within the basal ganglia appear to play a role in the processing of rhythm. One such region is the putamen, a round structure near the centre of the brain. Studies measuring levels of brain activity have found that the putamen is active when a person is listening to a beat. However, it is not clear whether the putamen is merely identifying the presence of the beat, or whether it is actually helping us to recreate that beat in our minds.

How can we tell what the putamen is doing?

Jessica Grahn and James Rowe designed a study which allowed them to distinguish between these two possibilities. They began their work by creating small snippets of sound. Some of the sound-bites contained a beat, while others did not. These ‘non beat’ sound-bites involved sounds which were not arranged in any rhythmic order. The researchers then combined the order of the sound-bites to create different sequences. These sequences fell into one of four key groups: (1) no beat, (sequences with no beat present), (2) new beat, (sequences in which participants heard a non beat followed by a beat), (3) beat continuation, (sequences with two versions of the same beat), and

(4) beat adjustment, (sequences where the original beat got faster or slower).

The researchers asked the participants to listen to the different sequences whilst a scanner measured how their brain responded. In order to measure this brain activity, they used functional magnetic resonance imaging, often know as fMRI. This is a form of brain imaging that allows us to see which regions of the brain are involved in which tasks. It does this by measuring the amount of oxygen that a specific brain region is using relative to other regions. If a region is using a lot of oxygen, it suggests that the region is ‘active’, that is, it’s involved in carrying out the task.

Image Source: Shutterstock Copyright: GrandeDuc

What did the researchers find?

They found that the putamen responded differently to different beat sequences. When there was no beat, the putamen wasn’t active. Similarly, when participants heard a new beat, the putamen didn’t respond. By contrast, when participants heard the same beat twice, the putamen was highly active. It was also active, but to a lesser extent, when the sequence involved the same beat played at different speeds.

These results suggest that the putamen was not responding to the presence of a beat per se, but was processing the continuation of the beat across the sequence. This supports the theory that the putamen is involved in our ability to recreate a beat in our minds.

Why is this important?

Prior to this study, researchers knew that the putamen was related to beat processing, but they didn’t know what its specific role was. This study showed that the putamen is important for the mental generation of a beat.

In addition to advancing our knowledge of the putamen’s role in beat processing, these findings have notable clinical implications. People with Parkinson’s disease are capable of identifying a beat in a piece of music, but have difficulty when it comes to reproducing the beat in their own minds. The research shows that this pattern of symptoms could be caused by damage to the putamen. Consequently, it highlights the necessity of focusing on the putamen as a target for future treatment of Parkinson’s disease.

This summary by Elizabeth Kirkham was shortlisted for Access to Understanding 2014 and was awarded first place. It describes research published in the following article, selected for inclusion in the competition by the Medical Research Council:

Finding and feeling the musical beat: Striatal dissociations between detection and prediction of regularity

PMCID: PMC3593578

J.A. Grahn & J.B. Rowe.

Cerebral Cortex (2013) 23(4), 913-921.

Access to Understanding entrants are asked to write a plain English summary of a research article. For Access to Understanding 2014 there were 10 articles to choose from, selected by the Europe PMC funders. The articles are all available from Europe PMC, are free to read and download, and were supported by one or more of the Europe PMC funders.

Look out here and on Twitter @EuropePMC_news for further competition news and other Europe PMC announcements.   

"Can you read my mind?"

By Elizabeth Kirkham, PhD student at the University of Sheffield

Note: Elizabeth was the winner of this year's Access to Understanding competition. Check back tomorrow to read her winning entry! It has also been published by eLife. Congratulations Elizabeth!

My background is in psychology, which means that over the years I’ve learned to steel myself against the inevitable question: “Can you read my mind?” Unfortunately, my ability to produce a witty reply is only slightly better than my ability to read minds, so an awkward pause is pretty much the best my questioner can hope for. Undoubtedly many of those asking this question are joking (though I can’t be sure, I can’t read their minds). Nevertheless, when the first thing that people associate with psychology is something psychologists can’t actually do, it’s clear that something needs to change.

This change won’t materialise unless the wider public see what it is we really do all day. Open access publications, which allow people to read papers without a subscription fee or one off payment, are a great start to making science more accessible to everybody. However, the presence of jargon can make these publications difficult to follow – even scientists within the same broad field can struggle to understand the terms used in their colleagues’ publications. 

Scientific knowledge is advancing rapidly, fueled by the advent of new technologies. Research as a discipline is also progressing, having undergone fundamental changes over the past two decades.  Thanks to these developments, the previously arduous process of searching for information has been condensed into seconds; instead of skimming through pages and pages of books and journals, we can find hundreds of relevant articles merely by pressing a few keys. Scientific research is expanding. Findings are no longer hidden within the walls of universities and libraries, but accessible to millions of people around the world.

However, finding information and comprehending its meaning are often two very different things. This theme was at the heart of the Access to Understanding ceremony 2014. The speeches given by Sir Mark Walport (Chief Scientific Advisor to the Government) and Sharmila Nebhrajani (CEO of AMRC and chair of judging panel), among others, highlighted the need for more people who can translate research articles into accessible language. Additionally, we as scientists can make our research available to a wider audience, by working on plain English summaries and clear explanations of our findings. My own field, Cognitive Neuroscience, is only a few decades old, but has already facilitated huge leaps forward in our understanding of the human brain. That said, expanding knowledge within the academic community is one thing, translating it into real change is quite another.

Elizabeth Kirkham receives her first place award

from Sir Mark Walport, 24 March 2014

I hope that initiatives like Access to Understanding will continue in their endeavours to make science accessible to a broader audience. The power of scientific discovery should not be stifled by an inability to communicate its relevance beyond the laboratory. Perhaps wider communication could also save future generations of psychologists from having to answer that dreaded question. After all, even if we could read minds, we’d never get the ethical approval to do so.

Can a garbage strike in nerve cells cause Parkinson's disease?

Image design: Serial/Trash

New research challenges common beliefs about the origin of the disease and draws attention to the nerve cells’ ability to tidy up.

Parkinson’s disease is a devastating neurological disorder where nerve cells in the brain slowly degenerate and die. The disease especially affects a certain type of nerve cell, the dopaminergic nerve cells, which are located in a small area of the brain called the substantia nigra. The dopaminergic nerve cells here are very important for motor function and as the number of nerve cells decrease, the patients are affected by debilitating tremors and mobility problems. Actor and Parkinson’s patient Michael J. Fox describes it “like having a 4-year-old child climbing around on your lap all the time, pulling on your arms and legs.”¹

Despite many years of research the exact cause of Parkinson’s disease is still unknown. One thing we know for certain is that the dopaminergic nerve cells build-up clumps of protein and leftover material, called Lewy bodies. The major component of Lewy bodies is a-synuclein, a protein therefore thought to be a primary causative factor for Parkinson’s disease. The fact that mutations in the a-synuclein gene increase the risk of developing Parkinson’s disease supports this theory.

Garbage disposal and power plants

Another suspect thought to play a role in Parkinson’s disease is the proteasome; a big protein complex, which is part of the cells “garbage disposal” system and can degrade non-functional proteins.

If unusable proteins are not disposed of, they clutter up the nerve cell and can form so-called pale bodies. These are small precursors of Lewy bodies.

Pale bodies and Lewy bodies are actually thought to protect the nerve cell by gathering the non-functional proteins in areas where they cannot disturb important processes in the nerve cell – akin to hiding your mess in the closet to prevent it from cluttering up your room. It is, however, only a temporary solution and eventually the nerve cells die.

A third culprit is the mitochondria; the cell’s power plants, which have numerous functions including production of energy from glucose. Extensive research points to dysfunctional mitochondria as a major contributor to Parkinson’s disease. For one thing, worn-out mitochondria are a large component of pale bodies.

Image Source: Shutterstock Copyright: Mopic

Modified mice

To investigate the interaction between a-synuclein, proteasomes and mitochondria researchers from the University of Nottingham used genetically modified mice. The DNA of the mice was changed so that certain genes were not expressed. This allowed the researchers to evaluate the exact effect of the proteins that the genes encoded. The research group had previously developed mice, which could not produce the most commonly used form of proteasomes, the 26S proteasomes, in their dopaminergic nerve cells. The garbage disposal system in these mice therefore did not work properly and they quickly developed extensive nerve cell death and pale bodies comparable to the ones seen in Parkinson’s patients.

The research group then set out to explore the importance of a-synuclein in this process. They did this by modifying the mice further, to obtain mice that in addition could not produce a-synuclein. This made it possible for them to compare the mice that lacked both 26S proteasomes and a-synuclein with the mice that only lacked 26S proteasomes. Surprisingly they found no differences: both type of mice showed equal amounts of nerve cell death and pale bodies. Since a-synuclein is thought to be essential to this process, the predicted outcome would be that the mice lacking a-synuclein are less affected and have lower amounts of pale bodies. This however is not the case.

In addition to looking at the amount of pale bodies, they also examined the content of the pale bodies and found it to be the same with or without a-synuclein. As expected they found the main component of the pale bodies to be the third suspected contributor to Parkinson’s disease: mitochondria. This points to a link between inefficient proteasomes and lacking disposal of worn-out mitochondria.

The role of a-synuclein

The surprising conclusion of this study is that a-synuclein is not essential for the development of pale bodies and that lack of functional proteasomes alone can lead to neurodegeneration in mice. More research is needed to tell if the pale bodies seen in the mice will develop into Lewy bodies and especially, if the results can be transferred to human nerve cells. If they can, it means that researchers studying Parkinson’s disease might have to re-evaluate their whole idea of how the disease originates. Instead of seeing a-synuclein as a primary causative factor, it might just be one of the major contributors along with others like proteasome and mitochondria dysfunction. This is of great importance for understanding the cause of Parkinson’s disease and development of new effective treatments in the future.

1. http://nexneuro.com/2010/02/11/michael-j-foxs-personal-battle/

This summary by Helle Bogetofte was shortlisted for Access to Understanding 2014 and was commended by the competition judges. It describes research published in the following article, selected for inclusion in the competition by Parkinson’s UK:

Pale body-like inclusion formation and neurodegeneration following depletion of 26S proteasomes in mouse brain neurones are independent of α-synuclein

PMCID: PMC3559752

S. M. L. Paine, G. Anderson, K. Bedford, K. Lawler, R. J. Mayer, J. Lowe and L. Bedford.

PLoS One (2013) 8(1), e54711

Access to Understanding entrants are asked to write a plain English summary of a research article. For Access to Understanding 2014 there were 10 articles to choose from, selected by the Europe PMC funders. The articles are all available from Europe PMC, are free to read and download, and were supported by one or more of the Europe PMC funders.

Look out here and on Twitter @EuropePMC_news for further competition news and other Europe PMC announcements.