Tagged: proteasome

DUBstop: Oxford-style

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This week multiple research groups at the University of Oxford and Boston-based FORMA Therapeutics announced a collaboration to identify, validate and develop deubiquitinating enzyme (DUB) inhibitors for the treatment of neurodegenerative conditions, like Parkinson’s.

But what exactly are DUB inhibitors? And how do they work?

In today’s post, we will answer these questions, look at what the new collaboration involves, and look at what else is happening with DUB inhibitors for Parkinson’s.


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Source: Blog4dubstep

Dubstep is a genre of electronic dance music that originated in South London in the late 1990s. Only recently -in the 2010s – has the culture really become more mainstream. And while I have a hard time appreciating the heavy bass music (man, I am becoming a grumpy old man before my time), it is amazing to watch some of the dancers who robotically embody this form of music:

The guy on the right is named Marquese Scott. Sometimes he simply defies the laws of physics.

The title of today’s post is a play on words, because rather than doing ‘Dubstep’ we are going to be discussing how to ‘DUB-stop’.

Researchers in Oxford have recently signed an agreement with a US company to focus resources and attention on a new approach for tackling neurodegenerative conditions, including Parkinson’s.

What they are proposing is a complicated biological dance.

Their idea: to stop deubiquitinating (DUB) enzymes.

What are deubiquitinating enzymes?

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Novartis focuses on improving PARKIN control

Last week, as everyone was preparing for Christmas celebrations, researchers at the pharmaceutic company Novartis published new research on a gene that is involved with Parkinson’s, called PARKIN (or PARK2).

They used a new gene editing technology – called CRISPR – to conduct a large screening study to identify proteins that are involved with the activation of PARKIN.

In today’s post we will look at what PARKIN does, review the research report, and discuss how these results could be very beneficial for the Parkinson’s community.


Source: Novartis

As many people within the Parkinson’s community will be aware, 2017 represented the 200th anniversary of the first report of Parkinson’s disease by James Parkinson.

It also the 20th anniversary of the discovery of first genetic mutation (or variant) that increases the risk of developing Parkinson’s. That genetic variation occurs in a region of DNA (a gene) called ‘alpha synuclein’. Yes, that same alpha synuclein that seems to play such a critical role in Parkinson’s (Click here to read more about the 20th anniversary).

In 2018, we will be observing the 20th anniversary of the second genetic variation associated with Parkinson.

That gene is called PARKIN:

Title: Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.
Authors: Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N
Journal: Nature. 1998 Apr 9; 392(6676):605-8
PMID: 9560156

In 1998, Japanese researchers published this report based on 5 individuals from 4 Japanese families who were affected by juvenile-onset Parkinson’s. In family 1, the affected individual was a female, 43 years old, born of first-cousin parents, and her two younger brothers are healthy. Her condition was diagnosed in her teens and it had then progressed very slowly afterwards. Her response to L-dopa was very positive, but L-dopa-induced dyskinesia were frequent. In family 2-4, affected individuals (born to unrelated parents) exhibited very similar clinical features to the subject in family 1. The age of onset was between 18 to 27 years of age.

Using previous research and various techniques the investigators were able to isolate genetic variations that were shared between the 5 affected individuals. They ultimately narrowed down their search to a section of DNA containing 2,960 base pairs, which encoded a protein of 465 amino acids.

They decided to call that protein PARKIN.

PARKIN Protein. Source: Wikipedia

How much of Parkinson’s is genetic?

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