Monday, March 16, 2009

PINK1 Research from London

Why do dopamine cells die?

Here's the problem, we read all of these articles and abstracts and try to make some sense of them but sometimes we find our eyes crossing as the confusion and profusion of terminology mounts. Our goal today is really to talk about the significance of the PINK1 gene and recent research at the Institute of Neurology, London under Dr Andrey G Abramov.

There are several genes which have been identified as being linked to family PD - inherited Parkinson's. Many of these genes "write the code" for the proteins which target the mitochondria. Mutations or misfolding of proteins of PINK1 cause an inherited form of PD identified as an autosomal recessive young onset form of Parkinson's disease. The PINK1 gene is specific to the mitochondria.

Mitochondria = an organelle which is part of a cell - just as an organ is to the body. Some cells have just one while others have thousands.
They power the cell by generating chemical energy in the form of adenosine triphospate (ATP) by converting food molecules into ATP.
And that's not all they do.
They are involved in maintaining proper chemical balances within the cells. They are also involved in signaling, a cellular form of grad school whereby a less specialized cell becomes more specialized. Those cells get their doctorates when they become pluripotent.

Mitochondrial proteins will vary depending upon the tissue type. In PINK1 the protein is serine/theronine kinease.

The mitochondria has two walls, the inner and the outer membrane. The outer membrane is easily permeable to small molecules such as ions and sugars. Large molecules need to have know the password, or to have the correct garage door opener signal if you prefer, in order to be transported through the outer membrane. And then things start to get tricky.

How does this relate to PD? First the bad news. In their role as chemical balancers, mitochondria must maintain the proper calcium level of the cell. Abnormal calcium levels have shown to be toxic to neurons. When the PINK1 gene was studied it was learned that its loss resulted in an abnormal calcium overload within the mitochondria. This calcium overload causes "the production of a dangerous reactive oxygen species that interfered with the ability of the mitochondria to transport sugar for energy production."

A normal PINK1 would be able to handle a calcium overload as that is part of their function. Once they malfunction, they are prone to making the dopamine neurons more vulnerable and may indeed cause their deaths.The good news is that Dr Andrey Abramov and his co-researchers at the Institute Neurology, London, UK have a better understanding of why certain dopamine neurons die.

reference: Cell Press 3/13/09 Molecular Cell

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