Thursday, 25 April 2013

Gretchen Amphlet Parkinson's UK lecture 2013 - Part 3

For Part 1: http://dialoguewithdisability.blogspot.co.uk/2013/04/gretchen-amphlet-parkinsons-uk-lecture.html


Understanding why nerve cells die in Parkinson’s - Case Studies

What are the faulty proteins doing to cause nerve cells to die? Two studies were presented that examined the role of two genes.

1. a-synuclein

When proteins are made the string of amino acids fold around each other to form a 3D shape: the shape determines a protein's function. Mutations have been found in the a-synuclein gene that cause misfolding of a-synuclein protein. Misfolded protein sticks together to form large cellular structures called Lewy bodies, leading to cell death and Parkinson's.

The same process of DNA encoding proteins via RNA that occurs in humans also occurs in flies (indeed in all living things). This makes it possible to transplant a mutant form of the human a-synuclein gene into flies to trick fly cells into making mutant a-synuclein protein. This causes the formation of Lewy bodies, loss of nerve cells and Parkinson-like motor impairment in flies. Interestingly, also producing normal human Rab11 protein (involved in moving proteins to the cell surface) in these Parkinson's flies dismantles the Lewy bodies, prevents nerve cell death and reverses some Parkinson’s symptoms.

2. dj1

Mitochondria are structures within cells. They are the power plants that produce all the energy needed by the cell. A toxic by-product of energy manufacture is "reactive oxidative species" (ROS), a chemical that can harm the cell. Nerve cells of the substantia nigra, which are lost in Parkinson's, require lots of energy; therefore they produce lots of ROS and are under "stress" to get rid of them before they damage the cell. Damaged cells trigger apoptosis (or “programmed cell death” where cells sacrifice themselves for the greater good) and die. A gene, dj1, helps the cell to clean up ROS. Perhaps unsurprisingly, mutations in dj1 have been found in Parkinson's sufferers; loss of dj1 function results in excessive ROS-induced cell damage, apoptosis and cell death. 

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