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”

Mdivi-1: the small molecule that could?

Mitochondrial division inhibitor-1 (mdivi-1) is a small molecule drug that is demonstrating very impressive effects in preclinical models of Parkinson’s disease. With further research it could represent a potential future therapy for people with Parkinson’s disease, particularly those with genetic mutations affecting the mitochondria in their cells. 

What are mitochondria?

In this post, we will explain what mitochondria are, how they may be involved in Parkinson’s disease, and we will discuss what the results of new research mean for future therapeutic strategies.


 

Mitochondria are fascinating.

Utterly. Utterly. Fascinating.

On the most basic level, Mitochondria (mitochondrion, singular; from the Greek words mitos (thread) and chondros (granule)) are just tiny little bean-shaped structures within the cells in our body, and their primary function is to act as the power stations. They supply the bulk of energy that cells require to keep the lights on. This chemical form of energy produced by the mitochondria is called adenosine triphosphate (or ATP). Lots of mitochondria are required in each cell to help keep the cell alive (as is shown in the image below, which is showing just the mitochondria (red) and the nucleus (blue) of several cells).

Lots of mitochondria (red) inside cells (nucleus in blue). Source: Clonetech

That’s the basic stuff – the general definition you will find in most text books on biology.

But let me ask you this:

How on earth did mitochondria come to be inside each cell and playing such a fundamental role?

I don’t know. Are you going to tell me?

No.

Why not?

Because we simply don’t know.

But understand this: Mitochondria are intruders.

Continue reading “Mdivi-1: the small molecule that could?”