TGF-beta: The Parkinson’s superfamily?

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A lot of Parkinson’s research has focused on a neurotrophic factor called glial cell-derived neurotrophic factor (or GDNF).

But GDNF only represents a small fraction of a much larger class of neurotrophic factors, called the Transforming growth factor-β (TGF-β) superfamily.

Recently, researchers have been investigating some of the other TGF-β family members in preclinical models of Parkinson’s and they have been making some interesting discoveries.

In today’s post, we will discuss what is meant by neurotrophic factor, explore who else is in the TGF-β superfamily, and look at two recent reports highlighting family members in the context of Parkinson’s.

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Different types of cells in the brain. Source: Dreamstime

Glial cells are the support cells in the brain. While neurons are considered to be the ‘work horses’ of neurological function – passing messages and storing memories – glial cells are in the background making sure that neurons are protected and well nurtured.

There are different types of glial cells, including astrocytes, oligodendrocytes and microglia. And each type has a specific function, for example microglia are the brain’s resident immune cells checking up on the health of the neurons while oligodendrocytes provide the neurons with a protective covering (called myelin sheath) which also helps to speed up the signalling of neurons.

A human astrocyte. Source: Wikipedia

Astrocytes provide nutrients and neurotrophic factors to neurons and make sure the environment surrounding the neurons is balanced and supportive. Glial cells are absolutely critical to the normal functioning of the brain.

What are neurotrophic factors?

Continue reading “TGF-beta: The Parkinson’s superfamily?”

When undruggable becomes druggable

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.


Source: PPcorn

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.
PMID: 9092472

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?

Continue reading “When undruggable becomes druggable”