Trying to LIMP-2 the lysosome

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Lysosomes are small bags of enzymes that are used to break down material inside of cells – digesting newly absorbed food or recycling old/used proteins and rubbish. Recently researchers have been discovering increasing evidence that points towards dysfunction in lysosomes as a key influential player in neurodegenerative conditions, like Parkinson’s.

There are several Parkinson’s genetic risk factors associated with lysosomal function (GBA being the obvious one), that can increase one’s risk of developing Parkinson’s.

But there is also data indicating that individuals without any of these risk factors may also have reduced lysosomal activity. And recently researchers have identified one possible explanation.

In today’s post, we will explore what lysosomes are, investigate how they maybe involved with Parkinson’s, review what the new data reports, and discuss how this information might be useful.

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Type of endocytosis. Source: Slidemodel

On a continual basis, cells inside your body are absorbing material from the world around them with the aim of collecting all that they need to survive. They do this predominantly via a process called endocytosis, in which a small part of the cell membrane envelopes around an object (or objects) and it is brought inside the cell.

As the section of cell membrane enters the interior of the cell, it detaches from the membranes and forms what is called an endosomes (sometimes it is also called a vacuole). Once inside, the endosome transported deeper into the interior of the cells where it will bind to another small bag that is full of digestive enzymes that help to break down the contents of the endosome.

This second bag is called a lysosome.

Lysosomes

How lysosomes work. Source: Prezi

Once bound, the lysosome and the endosome/vacuole will fuse together and the enzymes from the lysosome will be unleashed on the material contained in the vacuole. The digestion that follows will break down the material into more manageable components that the cell needs to function and survive.

This enzymatic process works in a very similar fashion to the commercial products that you use for washing your clothes.

Enzymatic degradation. Source: Samvirke

The reagents that you put into the washing machine with your clothes contain a multitude of enzymes, each of which help to break down the dirty, bacteria, flakes of skin, etc that cling to your clothes. Each enzyme breaks down a particular protein, fat or such like. And this situation is very similar to the collection of enzymes in the lysosome. Each enzyme has a particular task and all of them are needed to break down the contents of the endosome.

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

Continue reading “Trying to LIMP-2 the lysosome”

Happy birthday: Silverstein Foundation

Over the last 12 months, the Silverstein Foundation has quickly established itself as a major focused force in the fight against Parkinson’s.

And when I say ‘focused’, I mean ‘focused’ –  the foundation is “actively pursues and invests in cutting edge research with the goal of discovering new therapies for the treatment of Parkinson’s Disease in glucocerebrosidase (GBA) mutation carriers”.

But the output of this effort may well have major benefits for the entire Parkinson’s community.

In today’s post, we will discuss what GBA is, how it functions inside cells, its association with Parkinson’s, and what all of this GBA focused research being funded by the Silverstein Foundation could mean for the Parkinson’s community.


Jonathan Silverstein. Source: Forbes

This is Jonathan Silverstein.

He’s a dude.

He is also a General Partner and a Co-Head of Global Private Equity at OrbiMed – the world’s largest fully dedicated healthcare fund manager. During his time at OrbiMed, the company has invested in healthcare companies that have been involved with over 60 FDA approved products.

In February 2017, he was diagnosed with Parkinson’s disease at just 49 years of age.

Rather than simply accepting this diagnosis, however, Mr Silverstein decided to apply the skills that he has built over a long and successful career in funding biotech technology, and in March 2017, he and his wife, Natalie, set up the Silverstein Foundation.

They raised $6 million from donors and then provided another $10 million of their own money to fund the endeavour, which has funded a dozen research projects and started a new company called Prevail Therapeutics (we’ll come back to this shortly).

Source: Businesswire

The foundation has just one mission: “to actively pursue and invest in cutting edge research with the goal of discovering new therapies for the treatment of Parkinson’s Disease in GBA mutation carriers”

And it seeks to address this by achieving three goals:

  1. to find a way to halt the progression of Parkinson’s with GBA.
  2. to identify regenerative approaches to replace the damaged/lost cells
  3. to find preventative measures

What is ‘GBA’?

Continue reading “Happy birthday: Silverstein Foundation”

When GCase is away, the GSLs will play

 

 

New research published in the last week provides further experimental support for numerous clinical trials currently being conducted, including one by the biotech company Sanofi Genzyme.

Researchers have demonstrated that tiny proteins which usually reside on the outer wall of cells could be playing an important role in the protein clustering (or aggregation) that characterises Parkinson’s

In today’s post we will look at this new research and discuss what it could mean for the on going clinical trials for Parkinson’s. 


Source: Stevedalepetworld

The proverb ‘When the cat is away, the mice will play’ has Latin origins.

Dum felis dormit, mus gaudet et exsi litantro (or ‘When the cat falls asleep, the mouse rejoices and leaps from the hole’)

It was also used in the early fourteenth century by the French: Ou chat na rat regne (‘Where there is no cat, the rat is king’).

And then Will Shakespeare used it in Henry the Fifth(1599), Act I, Scene II:

Westmoreland, speaking with King Henry V, Gloucester, Bedford, Exeter and Warwick
“But there’s a saying very old and true,
‘If that you will France win,
Then with Scotland first begin:’
For once the eagle England being in prey,
To her unguarded nest the weasel Scot
Comes sneaking and so sucks her princely eggs,
Playing the mouse in absence of the cat,
To tear and havoc more than she can eat”

The phrase first appears in its modern form in the United States in the literary and political magazine The Port folio in 1802 (2; 323):

Interesting. But what does any of this have to do with Parkinson’s?

Continue reading “When GCase is away, the GSLs will play”