New research from multiple independent research groups proposes that one Parkinson’s associated protein (LRRK2) may be affecting the activity of another Parkinson’s associated protein (GCase).
Specifically, when LRRK2 becomes hyperactive (as is the situation in some cases of Parkinson’s), it causes is associated with a reduction in the amount of GCase activity.
In today’s post, we will discuss what LRRK2 and GCase both do, what the new research suggests, and how this news could influence efforts to treat Parkinson’s in the future.
Connections. Source: Philiphemme
For a long time, the Parkinson’s research community had a set of disconnected genetic risk factors – tiny errors in particular regions of DNA that were associated with an increased risk of developing Parkinson’s – but there seemed to be little in the way of common connections between them.
Known genetic associations with PD. Source: PMC
The researchers studied the biological pathways associated with these risk factors, trying to identify potential therapeutic angles as well as looking for connections between them.
The therapies are currently being clinically tested (Click here to read more about these), but the connections have taken a lot longer to find.
Recently one important connection has been identified by several research groups and it could have important implications for how Parkinson’s will be treated in the future.
What’s the connection?
Not a week goes by without some new peice of research suggesting yet another biological mechanism that could be useful in slowing or stopping Parkinson’s. This week researchers in Chicago reported that pharmacologically inhibiting a specific enzyme – farnesyltransferase – may represent a novel means of boosting waste disposal and helping stressed cells to survive.
A number of farnesyltransferase inhibitors are being developed for cancer, and there is the possibility of repurposing some of them for Parkinson’s.
In today’s post, we will discuss what farnesyltransferase is and does, what the new research report found, and we will consider whether inhibition of this biological pathway is do-able for Parkinson’s.
I am in the midst of preparing the “end of year review” and “road ahead” posts for 2019/2020 (they take a while to pull together). But it is already extremely apparent that we have an incredible amount of preclinical data piling up,…. and a serious bottleneck at the transition to clinical testing.
It is actually rather disturbing.
Previously this was a concern, but going forward – as more and more novel preclinical work continues to pile up – one can foresee that it is going to be a serious problem.
But there is just SOOOO much preclinical data on Parkinson’s coming out at the moment. Every single week, there is a new method/molecular pathway proposed for attacking the condition.
A good example of this frenetic pace of preclinical research is a recent report from researchers in Chicago, who discovered that a farnesyltransferase inhibitor could be beneficial in Parkinson’s.
New research published in the last week provides further experimental support for numerous clinical trials currently being conducted, including one by the biotech company Sanofi Genzyme.
Researchers have demonstrated that tiny proteins which usually reside on the outer wall of cells could be playing an important role in the protein clustering (or aggregation) that characterises Parkinson’s.
In today’s post we will look at this new research and discuss what it could mean for the on going clinical trials for Parkinson’s.
The proverb ‘When the cat is away, the mice will play’ has Latin origins.
Dum felis dormit, mus gaudet et exsi litantro (or ‘When the cat falls asleep, the mouse rejoices and leaps from the hole’)
It was also used in the early fourteenth century by the French: Ou chat na rat regne (‘Where there is no cat, the rat is king’).
And then Will Shakespeare used it in Henry the Fifth(1599), Act I, Scene II:
Westmoreland, speaking with King Henry V, Gloucester, Bedford, Exeter and Warwick
“But there’s a saying very old and true,
‘If that you will France win,
Then with Scotland first begin:’
For once the eagle England being in prey,
To her unguarded nest the weasel Scot
Comes sneaking and so sucks her princely eggs,
Playing the mouse in absence of the cat,
To tear and havoc more than she can eat”
Interesting. But what does any of this have to do with Parkinson’s?
Antidepressants are an important class of drugs in modern medicine, providing people with relief from the crippling effects of depression.
Recently, research has suggested that some of these drugs may also provide benefits to people suffering from Parkinson’s disease. But by saying this we are not talking about the depression that can sometimes be associated with this condition.
This new research suggests anti-depressants are actual providing neuroprotective benefits.
In today’s post we will discuss depression and its treatment, outline the recent research, and look at whether antidepressants could be useful for people with Parkinson’s disease.
It is estimated that 30 to 40% of people with Parkinson’s disease will suffer from some form of depression during the course of the condition, with 17% demonstrating major depression and 22% having minor depression (Click here to read more on this).
This is a very important issue for the Parkinson’s community.
Depression in Parkinson’s disease is associated with a variety of poor outcomes not only for the individuals, but also for their families/carers. These outcomes can include greater disability, less ability to care for oneself, faster disease progression, reduced cognitive performance, reduced adherence to treatment, worsening quality of life, and increased mortality. All of which causes higher levels of caregiver distress for those supporting the affected individual (Click here to read more about the impact of depression in early Parkinson’s).
What is depression?
Wikipedia defines depression as a “state of low mood and aversion to activity that can affect a person’s thoughts, behaviour, feelings, and sense of well-being” (Source). It is a common mental state that causes people to experience loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep or appetite, low energy, and poor concentration.
Importantly, depression can vary significantly in severity, from simply causing a sense of melancholy to confining people to their beds.
What causes depression?