Is Parkinson’s A Prion Disease?

By Neuroskeptic | October 14, 2017 2:45 pm

The Journal of Neuroscience recently featured a debate over the hypothesis that Parkinson’s disease is, at least in some cases, caused by a prion-like mechanism – misfolded proteins that spread from neuron to neuron.

A prion is a protein that has taken on an abnormal shape and that can spread itself by making other, healthy molecules of the same protein adopt its abnormal configuration. The best-known prion disease is variant CJD aka “mad cow disease”, but some researchers believe that Parkinson’s is also a prion-like disorder.

The evidence is reviewed by Patrik Brundin and Ronald Melki in a Journal of Neuroscience paper. In an accompanying article, Surmeier et al. put the case that the prion theory can’t explain everything about Parkinson’s. The journal call this debate format ‘Dual Perspectives’.

Brundin and Melki argue that there is good evidence suggesting that a protein called alpha-synuclein (α-SYN) can become prion-like, and that this causes at least some Parkinson’s cases. α-SYN is produced in large quantities by all neurons. The authors say that a α-SYN misfolding event can occur, by chance, in any neuron, although it seems especially likely to occur in the cells of the olfactory bulb or the vagus nerve.

Once the rogue α-SYN exists, it spreads itself from neuron to neuron and thus progressively ‘infects’ the brain. The disordered α-SYN forms clumpy aggregates called Lewy bodies, and eventually kills neurons, causing the symptoms of Parkinson’s.parkinson_prion

Key evidence for the prion hypothesis, Brundin and Melki say, is the fact that brain tissue from Parkinson’s patients can ‘transmit’ the disease to animals when injected into their brains. What’s more, when healthy donor brain cells were grafted into the brain of Parkinson’s patients as an experimental treatment, the donor cells sometimes developed Lewy bodies, as if they had been infected by the host brain.

In their counterpoint article, Surmeier et al. don’t deny the idea that α-SYN can behave like a prion under some conditions. The problem, they say, is that the progression of Lewy bodies through the brain in Parkinson’s disease doesn’t follow a prion-like pattern.

In Parkinson’s, one brain area (e.g. the substantia nigra) might show severe Lewy pathology while a nearby area, heavily connected to the first by synapses, shows none at all. Even within a given brain region, some cell types show degeneration (e.g. dopamine neurons) while others are entirely spared (e.g. GABA neurons.) This is hard to reconcile with the simple idea of α-SYN prions spreading like a contagion and causing damage wherever they go.

Surmeier et al. conclude that misfolded α-SYN may indeed be involved in Parkinson’s, but that it can only cause disease when the conditions are right. Most neurons, they say, are able to recognize and break down any rogue α-SYN, preventing aggregation. However, old age, environmental factors, and genetic risks could all weaken these defences. Substantia nigra dopamine neurons are especially vulnerable, Surmeier et al. say, because of their demanding workload in terms of constant, heavy “pacemaker” firing.

In other words, misfolded α-SYN might be harmless in itself, with Parkinson’s only arising when the usual defences against it break down.

This debate reminds me somewhat of the historical argument over the germ theory of disease. When it was proposed that microscopic germs were the cause of many diseases, there were sceptics. Some said that germ infection was just the symptom of underlying poor health. This ‘terrain theory’ has echoes in Surmeier et al.’s arguments.

Overall, these are both interesting papers and although it was a debate format, both sets of authors seemed fairly close in what they were arguing: that α-SYN prions are involved in Parkinson’s, but that some cells are more vulnerable to them than others.

CATEGORIZED UNDER: genes, papers, select, Top Posts
  • Jeremy Teman

    Misfolded alpha-synuclein does not “become a prion” since it was not a prion protein originally. Infectious proteins that are not prions are sometimes called “prion-like”.

    • Neuroskeptic

      Thanks, I have edited the post!

  • Paul Rain

    Hmm, although if we’re looking at historical analogies, folks in Japan, the country most affected by beriberi, thought that it must have an explanation in that new-fangled germ theory, right up until it was shown that it was caused by deficiencies in food.

    On the other hand, is this proof that boomers are brain eating zombies? I can believe that.

  • Uncle Al

    If Parkinson’s is a prion disease (thermodynamic rather than biologic source), then it is contagious. An added nucleation site will trigger crystallization of a supersaturated solution. In the case of enantiomorphic (benzil, molten 1,1′-binaphthyl) or polymorphic (glycine, ethylenediamine tartrate hydrate) crystals, the seed determines the product.

    Secure an animal (or Chinese prisoner) model, nucleate, observe.

    • American

      Not funny

  • Ed Gehrman

    “The PROBLEM with most Government and University informational websites is that no attempt is made to critique the research reports, making it impossible for others to understand the significance of these data. There is much controversy regarding the causality of TSEs. Our research shows that prion amyloid (the TSE research focus for the past 30 years) is the result of a bacterial infection. This controversy directly reflects on Louis Pasteur’s efforts to prove that replicating crystals are not the cause of infectious disease, but instead bacteria are the culprits. Too bad we have to rehash this controversy.” Visit for more information.

  • Parkinson’s Database Coalition

    Not a Prion disease…It’s far more likely to be a mistaken immune response. The body may be simply responding to false ‘distress calls’ from cells in the substantia nigra that perhaps originated from a long term underlying infection that has long since passed or even a simple mistake in the peptide chain leading to a type of apoptosis. Parkinson’s appears to modify itself with treatment, leading it to become degenerative. This suggests an immune response is in play. Some research has already shown that blocking the false immune reaction stops the disease dead in its tracks. This is why some liver drugs seem to be promising…but for how long will they work? None of this is characteristic of prion disease and could explain why nothing obviously ‘wrong’ shows up in a standard diagnostic workup. Most Parkinson’s patients are in unusually good health aside from the movement disorder. Parkinson’s is certainly not contagious, but could absolutely be a result of a prior bacterial or viral infection. The immune system just doesn’t know the infection is gone and continues to attack the cells. When the cells don’t respond to the normal defenses, the only solution the immune system has is to destroy the cells completely. Kind of a loose theory but it works.

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  • Ajit

    Curious to know whether patients of Kallman syndrome (anosmia owing to aplasia of the olfactory bulb and tracts in association with hypogonadism) are “protected” from PD

    • Neuroskeptic

      Good question! A quick PubMed search reveals no research…



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Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.


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