A-Synuclein: A pain in the gut?

pdgut[ropagation

This protein (alpha-synuclein) ‘folds’ out of shape and forms  sticky clumps (or aggregates) that fail to work properly and contribute to the formation of ‘lewy bodies,’ which invade the brain and lead to dementia. One question is: Does the formation of lewy bodies mean it is a protective mechanism like a scab that protects a wound and therefore is a good thing OR do the clumps of protein act as the villain, tearing our brains down and leading to dementia?

The conventional view of Parkinson’s disease (see the diagram above) is that it is the result of alpha-synuclein going from neuron to neuron like a virus and it starts in the nervous sytem of the gut, working its way upward until it finally gets into the brain. Lewy bodies (clumps of a-synuclein) appear in lower nerves before they show up in the brain, so it would appear to be an ‘open and shut case.’  But hold on a minute! Like most things PD-related it ain’t that simple!

Simone Engelender of the Technion-Israel Institute of Technology and Ole Isacson of Harvard Medical School pointed out that 47 percent of cases do not have an ascending progression and Lewy bodies often appear in higher nerve centers first. Their hypothesis as to why these contradictory results occur? They believe alpha-synuclein accumulation starts simultaneously all through the nervous system but, dependent on how well the nerve systems can handle toxicity, specific areas may present before or after other parts within the body. The two researchers assert that the gut has a nervous system less capable of tolerating toxicity so problems become apparent sooner, giving the impression that the outbreak originated in the gut.

This could change the ideas of some scientists that advocate cutting off the vagus nerve under the impression that this could stop (or slow down) the migration of a-synuclein clumps to the brain. If the above new hypothesis is proven beyond doubt then clearly cutting the vagus nerve would be a waste of time and a major rethink of similar procedures would be necessary.

C

 

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