GCase: Mutants matter?

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Tiny genetic variations in a region of DNA called the GBA gene are associated with an increased risk of developing Parkinson’s. The information in the GBA gene provides the instructions for making an enzyme (called GCase) which is involved with waste disposal inside of cells.

Individuals with Parkinson’s who carry a variation in their GBA gene typically have low levels of GCase activity, so researchers have been attempting to identify therapeutic molecules that will enhance the level and activity of GCase as an approach towards slowing the progression of Parkinson’s.

Recently, however, new research has provide novel insights into how the biology of GCase pathway may be affected in individuals with Parkinson’s who carry a GBA genetic variation. 

In today’s post, we will explain what the GBA gene and GCase enzyme are, review the new research, and consider the potential implications of these findings.

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Prof Sulzer. Source: Youtube

Professor David Sulzer is one individual in the scientific research community who truly fascinates me.

In addition to being at the absolute top of his game academically (he is a professor of Psychiatry, Neurology, Pharmacology at Columbia University and maintains a very large research group investigating neurodegenerative conditions), he is also a composer and musician with a discography that any professional artists would be extremely proud of (his recording alias is Dave Soldier).

He’s also written books (for example Music Math and Mind“).

Source: Twitter

Where he finds the time to do all of these thing I do not know, but I really like the combination of art and science.

Oh, and did I forget to mention the Thai Elephant Orchestra?

I’m sorry: The what?!?

Just watch:

They have released three CDs and the band grew up to 14 elephants.

Fascinating, but what does this have to do with Parkinson’s?

Continue reading “GCase: Mutants matter?”

The autoimmunity of Parkinson’s disease?

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In this post we discuss several recently published research reports suggesting that Parkinson’s disease may be an autoimmune condition. “Autoimmunity” occurs when the defence system of the body starts attacks the body itself.

This new research does not explain what causes of Parkinson’s disease, but it could explain why certain brain cells are being lost in some people with Parkinson’s disease. And such information could point us towards novel therapeutic strategies.


Nature_cover,_November_4,_1869

The first issue of Nature. Source: SimpleWikipedia

The journal Nature was first published on 4th November 1869, by Alexander MacMillan. It hoped to “provide cultivated readers with an accessible forum for reading about advances in scientific knowledge.” It has subsequently become one of the most prestigious scientific journals in the world, with an online readership of approximately 3 million unique readers per month (almost as much as we have here at the SoPD).

Each Wednesday afternoon, researchers around the world await the weekly outpouring of new research from Nature. And this week a research report was published in Nature that could be big for the world of Parkinson’s disease. Really big!

On the 21st June, this report was published:

Nature
Title: T cells from patients with Parkinson’s disease recognize α-synuclein peptides
Authors: Sulzer D, Alcalay RN, Garretti F, Cote L, Kanter E, Agin-Liebes J, Liong C, McMurtrey C, Hildebrand WH, Mao X, Dawson VL, Dawson TM, Oseroff C, Pham J, Sidney J, Dillon MB, Carpenter C, Weiskopf D, Phillips E, Mallal S, Peters B, Frazier A, Lindestam Arlehamn CS, Sette A
Journal: Nature. 2017 Jun 21. doi: 10.1038/nature22815.
PMID: 28636593

In their study, the investigators collected blood samples from 67 people with Parkinson’s disease and from 36 healthy patients (which were used as control samples). They then exposed the blood samples to fragments of proteins found in brain cells, including fragments of alpha synuclein – this is the protein that is so closely associated with Parkinson’s disease (it makes regular appearances on this blog).

What happened next was rather startling: the blood from the Parkinson’s patients had a strong reaction to two specific fragments of alpha synuclein, while the blood from the control subjects hardly reacted at all to these fragments.

In the image below, you will see the fragments listed along the bottom of the graph (protein fragments are labelled with combinations of alphabetical letters). The grey band on the plot indicates the two fragments that elicited a strong reaction from the blood cells – note the number of black dots (indicating PD samples) within the band, compared to the number of white dots (control samples). The numbers on the left side of the graph indicate the number of reacting cells per 100,000 blood cells.

Table1

Source: Nature

The investigators concluded from this experiment that these alpha synuclein fragments may be acting as antigenic epitopes, which would drive immune responses in people with Parkinson’s disease and they decided to investigate this further.

Continue reading “The autoimmunity of Parkinson’s disease?”