Every textbook written about the condition will tell you that the classical pathological characteristic of Parkinson’s is the loss of dopamine neurons in the midbrain region of the brain. It is the distinguishing feature that pathologists look for in order to provide a postmortem diagnosis of the condition.
But what is meant by the words ‘loss of dopamine neurons’? Do the cells actually die? Recently researchers from Korea have published new data exploring this question.
Interestingly, they found evidence of ‘dormant’ dopamine neurons in postmortem sections of brains from people with Parkinson’s – even those with severe forms of the condition.
In today’s post, we will discuss what a dopamine neuron is, what this new research found, and what it could mean for our understanding of Parkinson’s.
2019 represented the centenary year for an important discovery in Parkinson’s research.
In 1919, the Uzbek neuropathologist Konstantin Tretiakoff (1892-1958) reported his findings regarding an examination of 54 human brains.
Konstantin Tretiakoff. Source: Wikipedia
Six of the postmortem brains had belonged to individuals who had suffered from Parkinson’s and three others had been diagnosed with postencephalitic Parkinsonism. In these brains he noticed something rather striking.
What did he find?
Nuclear receptor related 1 protein (or NURR1) is a protein that has been shown to have a powerful effect on the survival of dopamine neurons – a population of cells in the brain that is severely affected by Parkinson’s.
For a long time researchers have been searching for compounds that would activate NURR1, but the vast majority of those efforts have been unsuccessful, leaving some scientists suggesting that NURR1 is “undruggable” (meaning there is no drug that can activate it).
Recently, however, a research report was published which suggests this “undruggable” protein is druggable, and the activator is derived from a curious source: dopamine
In today’s post, we will discuss what NURR1 is, what the new research suggests, and how this new research could be useful in the development of novel therapeutics for Parkinson’s.
It always seems impossible until it’s done – Nelson Mandela
In 1997, when Nelson Mandela was stepping down as President of the African National Congress, some researchers in Stockholm (Sweden) published the results of a study that would have a major impact on our understanding of how to keep dopamine neurons alive.
(Yeah, I know. That is a strange segway, but some of my recent intros have dragged on a bit – so let’s just get down to business)
Dopamine neurons are of the one groups of cells in the brain that are severely affected by Parkinson’s. By the time a person begins to exhibit the movement symptoms of the condition, they will have lost 40-60% of the dopamine neurons in a region called the substantia nigra. In the image below, there are two sections of brain – cut on a horizontal plane through the midbrain at the level of the substantia nigra – one displaying a normal compliment of dopamine neurons (on the left) and the other from a person who passed away with Parkinson’s demonstrating a reduction in this cell population (on the right).
The dark pigmented dopamine neurons in the substantia nigra are reduced in the Parkinsonian brain (right). Source:Memorangapp
The researchers in Sweden had made an amazing discovery – they had identified a single gene (a specific region of DNA) that was critical to the survival of dopamine neurons. When they artificially disrupted the section of DNA where this gene lives – an action which resulted in no protein for this gene being produced – it resulted in mice being born with no midbrain dopamine neurons:
Title: Dopamine neuron agenesis in Nurr1-deficient mice
Authors: Zetterström RH, Solomin L, Jansson L, Hoffer BJ, Olson L, Perlmann T.
Journal: Science. 1997 Apr 11;276(5310):248-50.
The researchers who conducted this study found that the mice with no NURR1 protein exhibited very little movement and did not survive long after birth. And this result was very quickly replicated by other independent research groups (Click here and here to see examples)
So what was this amazing gene called?
Nuclear receptor related 1 protein (or NURR1; it is also known as NR4A2 – nuclear receptor subfamily 4, group A, member 2)
And what is NURR1?
Aspirin is one of the oldest drugs in medical use today.
Recently researchers noticed something interesting about ‘low doses’ of aspirin that could have implications for Parkinson’s: It raises the amount of dopamine in the brain
Specifically, low doses of aspirin triggers an increase in the levels of an enzyme called tyrosine hydroxylase, which is involved in the production of chemical dopamine. Given that levels of dopamine are severely reduced in the brain of a person with Parkinson’s, this new result is kind of interesting.
In today’s post, we will have a look at what aspirin and tyrosine hydroxylase are, what the new research results report, and what this could mean for the Parkinson’s community.
The Ebers Papyrus (also known as the also known as Papyrus Ebers) is considered one of the most oldest medicinal “encyclopedias”.
It outlines 700 Egyptian medicinal formulas and remedies dating back to circa 1550 BC. We know nothing about who wrote the document (even the source of the papyrus is unknown – it may have been found with a mummy in the El-Assasif district of the Theban necropolis).
One thing is clear though: the people who wrote it were a very far sighted bunch.
Interestingly, the papyrus mentions use of Willow bark and Myrtle to treat fever and pain. Both of these plants are rich in Salicylic acid.
What is Salicylic acid?
It is an active precursor (or metabolite) of acetylsalicylic acid – which is also known as ‘Aspirin’.
What exactly is aspirin?