Turn back Bach?

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Cellular activity generates a lot of waste and by-products. Cells have developed very efficient methods of dealing with this situation.

As we age, however, these processes become strained, and in degenerative conditions they appear to be rather dysfunctional. 

New research highlights a novel mechanism – Bach1 derepression – which points towards a new class of potential therapeutics and interesting avenues of further study.

In today’s post, we will discuss the results of this new research and explore the implications of it.

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Source: Maxpixel

I am marveling at the fact that I am typing these words.

And that you are reading them.

Consider for a moment the requirements of this arrangement. And I’m not talking about the tiny muscles changing the size of the pupil in your eye, or the neurons in your visual cortex firing in unison to give you a correct and colour-rich representation of the world in front of you that has nothing to do with the actual content being observed.

Rather, I’m thinking more about about what is going on one level down – actually inside of each cell:

A liver cell. Source: Muhadharaty

There is a universe of frenzied molecular activity in each and every cell of our bodies. And we are only just starting to build up a user guide to the densely packed, fuzzy complexity of this inner world. This video gives an extremely simplified version of some of what is going on (in reality, the interior of cells is significantly more densely packed and the activity is a vastly quicker):

And as I suggested above it should be celebrated that what occurs in these cells is so rapid, efficient and precise that I can type these words and you can read them.

All of this crazy activity, however, produces waste and by-products.

Cells have of course developed very effective means of dealing with those issues. But as we age, cells can start to struggle with the task of waste disposal. And as a result, we can start to see an accumulation of these by-products, which can lead to stress on the cell, particularly in the form of oxidative stress.

What is oxidative stress?

Continue reading “Turn back Bach?”

CRISPR-Cas9: “New CRISPY Parkinson’s research”

Recently a Parkinson’s-associated research report was published that was the first of many to come.

It involves the use of a genetic screening experiment that incorporates new technology called ‘CRISPR’.

There is an absolute tidal wave of CRISPR-related Parkinson’s disease research coming down the pipe towards us, and it is important that the Parkinson’s community understands how this powerful technology works.

In today’s post we will look at what the CRISPR technology is, how it works, what the new research report actually reported, and discuss how this technology can be used to tackle a condition like Parkinson’s.


Me and my mother (and yes, the image is to scale). Source: Openclipart

My mother: Simon, what is all this new ‘crispy’ research for Parkinson’s I heard about on the news?

Me: Huh? (I was not really paying attention to the question. Terrible to ignore one’s mother I know, but what can I say – I am the black sheep of the family)

My mother: Yes, something about ‘crispy’ and Parkinson’s.

Me: Oh! You mean CRISPR. Yeah, it’s really cool stuff.

My mother: Ok, well, can you explain it all to me please, this ‘Crisper’ stuff?

Me: Absolutely.

CRISPR.101 (or CRISPR for beginners)

In almost every cell of your body, there is a nucleus.

It is the command centre for the cell – issuing orders and receiving information concerning everything going on inside and around the cell. The nucleus is also a storage bank for the genetic blueprint that provides most of the instructions for making a physical copy of you. Those grand plans are kept bundled up in 23 pairs of chromosomes, which are densely coiled strings of a molecule called Deoxyribonucleic acid (or DNA).

DNA’s place inside the cell. Source: Kids.Britannica

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Are we getting NURR to the end of Parkinson’s disease?

Nuclear receptor related 1 protein (or NURR1) is a protein that is critical to the development and survival of dopamine neurons – the cells in the brain that are affected in Parkinson’s disease.

Given the importance of this protein for the survival of these cells, a lot of research has been conducted on finding activators of NURR1.

In today’s post we will look at this research, discuss the results, and consider issues with regards to using these activators in Parkinson’s disease.


Comet Hale–Bopp. Source: Physics.smu.edu

Back in 1997, 10 days after Comet Hale–Bopp passed perihelion (April 1, 1997 – no joke; perihelion being the the point in the orbit of a comet when it is nearest to the sun) and just two days before golfer Tiger Woods won his first Masters Tournament, 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.

Dopamine neurons are one group of cells in the brain that are severely affected by Parkinson’s disease. 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 and the other from a person who passed away with Parkinson’s demonstrating a reduction in this cell population.

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The dark pigmented dopamine neurons in the substantia nigra are reduced in the Parkinson’s disease brain (right). Source:Memorangapp

The researchers in Sweden had made an amazing discovery – they had identified a single gene that was critical to the survival of dopamine neurons. When they artificially mutated the section of DNA where this gene lives – an action which resulted in no protein for this gene being produced – they generated genetically engineered mice with no 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 research groups (Click here and here to see examples)

So what was this amazing gene called?

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