So, there’s a new theory being proposed for Parkinson’s.  One that seems to fit the pieces pretty nicely.

And, the theory?  Folks with Parkinson’s disease have a garbage handling problem.  OK.  That may confuse you- but bear with me.

All of our cells choose homeostasis- if they are healthy.  That means that our cells are trying to maintain what we engineers call a steady state.  The state where the cell’s internal physico-chemical conditions are maintained at the optimal level. A steady state is when the behavior of the system are unchanging over time (not necessarily second by second, but certainly minute by minute).

Back to Parkinson’s.  The brain cells also have to clear waste products from within their cellular membranes, and that process is mediated by lysosomes.  (A lysosome is an organelle holding a bunch of degradative enzymes, that act like PAC-man chomping up the waste in the cells, rendering the material then able to be excreted from the cell membrane.)  In particular, the waste product that’s an issue with Parkinson’s is α-synuclein.

When α-synuclein doesn’t get removed from the neuron (the name for the nerve cells of the brain), it deviates from its normal structure; it becomes mis-folded and then clumps together  Those clumps are called Lewy Bodies (which include  cellular materials, as well).  As the Lewy Bodies accumulate, the neurons cease functioning and eventually die.

This problem may also be related to mitochondrial dysfunction.  (The mitochondria is an organelle that is the powerhouse of the cell.)  Some gene variants let the mitochondria produce reactive oxygen molecules among other compounds that damage the lysosome.  (This means waste removal is hampered or blocked within the cell.)

The Lewy Bodies are found in the substantia nigra, the region of the brain directly behind the eyes. And, that’s the region of the brain the produces dopamine (a neurotransmitter which regulates movement, learning, and mood.

Interestingly, the α-synuclein accumulation is not isolated to the brain- they also accumulate in the nasal cavity, throat nerves, and in our guts (at least in the guts of folks who manifest Parkinson’s)- particularly about the vagus nerve (which connects the gut to the brain).  (I’ve already reported on this pathway on my blog.    Should the vagal nerve-brain connection be severed [the idea was to preclude the formation of gastric ulcers], folks still manifest Parkinson’s disease. But, if there is a mutation in the PINK1 gene [critical to mitochondrial function], there is an uptick in early-onset Parkinson’s disease.)

What this really means is that drugs that have been (and are being) developed for lysosomal abnormalities could have tremendous utility in treating Parkinson’s patients.  One such drug is ambroxol.  (It is officially used to decrease the production of mucous in our respiratory tracts- but it also stops the buildup of excess lipids and proteins.)  But, most researchers are still sticking with α-synuclein as the primary driver for the disease (because of the prevalence of Lewy Bodies).

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