Inflammation is part of the immune system’s response to damage or infection. It is a very natural process that our bodies undergo when we come into harms way.
Researchers at the University of Queensland, have recently demonstrated something interesting about the inflammation associated with Parkinson’s: by inhibiting a very specific part of the inflammatory process, they can reduce the spread of Parkinson’s associated alpha synuclein pathology in models of PD.
And they have developed a drug – called MCC950 – that specifically targets that component of the inflammation process which they are now seeking to test in clinical trials.
In today’s post, we will discuss what inflammation is, review this new research, and consider what it could all mean for the Parkinson’s community.
Spot the unhealthy cell – exhibiting signs of stress (yellow). Source: Gettyimages
No silly preamble today – this is going to be a very long post, so we’re diving straight in:
When cells in your body are stressed or sick, they begin to release messenger proteins which inform the rest of your body that something is wrong.
When enough cells release these messenger proteins, it can cause inflammation.
What is inflammation?
Inflammation is a vital 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, 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 the level of messenger proteins being released partly depends on multi-protein structures called inflammasomes.
What are inflammasomes?
At the bottom of our previous post, we mentioned that Japan is the only country where women have a higher incidence of Parkinson’s disease than men.
We also suggested that we have no idea why this difference exists. Well, a study presented at the Cardiovascular, Renal and Metabolic Diseases conference in Annapolis City (Maryland) last week may now be able to explain why this is.
The prevalence of Alzheimer’s disease is significantly higher in women compared to men. One recent estimate suggested that almost two-thirds of individuals diagnosed with Alzheimer’s disease are women (More information here). One possible reason for this is that Alzheimer’s disease is a condition of the elderly and women live longer.
So why is it then is the exact opposite true in Parkinson’s disease???
Source: The Telegraph Newspaper
Men are approximately twice as likely to develop Parkinson’s disease as females (More information here)
In addition, women are on average diagnosed 2 years later than men (More information here)
This gender difference has long puzzled the Parkinson’s research community. But now a group from the University of North Texas Health Science Center think that they may have the answer.
The researchers – lead by Shaletha Holmes from Dr Rebecca Cunningham’s lab – observed that when they stressed dopamine neurons, adding the male hormone testosterone made the damage worse. Interestingly, they found that testosterone was doing this by acting on a protein called cyclooxygenase 2 (or COX2). When they blocked the actions of COX2 while stressing dopamine neurons, they found that they also blocked the damaging effect of testosterone. The researchers concluded that testosterone may exacerbate the damage (and death) in dopamine neurons that occurs in Parkinson’s disease, thus possibly explaining the sex differences described above.
Now, there are several interesting aspects to this finding:
Firstly, the use of Ibuprofen, the nonsteroidal anti-inflammatory drug used for relieving pain, has long been associated with reducing the risk of Parkinson’s disease (More information here).
Ibuprofen is a COX2 inhibitor.
But more importantly, several years ago it was shown that Japanese men have lower levels of testosterone than their Western equivalents. Here is the study:
Title: Evidence for geographical and racial variation in serum sex steroid levels in older men.
Authors: Orwoll ES, Nielson CM, Labrie F, Barrett-Connor E, Cauley JA, Cummings SR, Ensrud K, Karlsson M, Lau E, Leung PC, Lunggren O, Mellström D, Patrick AL, Stefanick ML, Nakamura K, Yoshimura N, Zmuda J, Vandenput L, Ohlsson C; Osteoporotic Fractures in Men (MrOS) Research Group.
Journal: Journal of Clinical Endocrinol. Metab. 2010 Oct;95(10):E151-60.
The study suggested that total testosterone levels (while similar in men from Sweden, Tobago and the US) were 16 per cent higher in men from Hong Kong and Japan. BUT – and here’s the catch – Japanese men also had higher levels of a testosterone-binding hormone (Sex hormone-binding globulin or SHBG), so there is less of the testosterone floating around free to act. As a result, Japanese men had the lowest levels of active testosterone in the study.
Intriguingly, the researchers found that Japanese men who emigrated to the US had similar testosterone levels to men of European descent, suggesting that environmental influences may be having an effect of testosterone levels. Diet perhaps?
If testosterone is found to play a role in the gender difference found in Parkinson’s disease, the lower levels of free testosterone observed in Japanese men may explain why women in Japan have a higher risk of Parkinson’s disease than men.
EDITOR’S NOTE: WHILE WE HAVE NO DOUBTS REGARDING THE RESEARCH OF DR CUNNINGHAM AND HER GROUP, WE ARE TAKING A LEAP IN THIS POST BY APPLYING THE TESTOSTERONE RESULTS TO THE GENDER DIFFERENCE IN JAPAN. THIS IS PURE SPECULATION ON OUR PART. WE HAVE SIMPLY SAT DOWN AND TRIED TO NUT OUT POSSIBLE REASONS AS TO WHY THERE IS A REVERSED GENDER DIFFERENCE FOR PARKINSON’S DISEASE IN JAPAN. OUR THEORY IS YET TO BE TESTED, AND MAY BE COMPLETELY BONKERS. WE PRESENT IT HERE PURELY FOR DISCUSSION SAKE AND WELCOME YOUR THOUGHTS.