This post contains material from an older one, updated based on new discoveries.
There are many things you don’t want gathering in large numbers, including locusts, rioters, and brain proteins. Our nerve cells contain many proteins that typically live in solitude, but occasionally gather in their thousands to form large insoluble clumps. These clumps can be disastrous. They can wreck neurons, preventing them from firing normally and eventually killing them.
Such clumps are the hallmarks of many brain diseases. The neurons of Alzheimer’s patients are riddled with tangles of a protein called tau. Those of Parkinson’s patients contain bundles, or fibrils, of another protein called alpha-synuclein. The fibrils gather into even larger clumps called Lewy bodies.
Now, Virginia Lee from the University of Pennsylvania School of Medicine has confirmed that the alpha-synuclein fibrils can spread through the brains of mice. As they spread, they corrupt local proteins and gather them into fresh Lewy bodies, behaving like gangs that travel from town to town, inciting locals into forming their own angry mobs. And as these mobs spread through the mouse brains, they reproduce two of the classic features of Parkinson’s disease: the death of neurons that produce dopamine, and movement problems.
This is the clearest evidence yet that alpha-synuclein can behave like prions, the proteins that cause mad cow disease, scrapie and Creutzfeld-Jacob disease (CJD). Prions are also misshapen proteins that convert the shape of normal peers. But there is a crucial distinction: prions are infectious. They don’t just spread from cell to cell, but from individual to individual. As far as we know, alpha-synuclein can’t do that.
People infected with the bird flu virus – influenza A subtype H5N1 – go through the usual symptoms of fever, aching muscles and cough. The virus is so virulent that 60% of infected humans have died. But according to a study in mice, the infection could also take a more inconspicuous toll on the brain, causing the sorts of damage that could increase the risk of diseases like Parkinson’s and Alzheimer’s many years after the virus has been cleared.
The link between influenza and Parkinson’s disease is hardly old but certainly controversial. Previous studies have found no traces of flu genetic material in Parkinson’s patients, but one of the strongest pieces of evidence for a link comes from analysing an outbreak of von Economo disease following the 1918 flu pandemic.
To date, 433 people have been infected with H5N1, and a few cases have shown problems with their nervous system, running the gamut from inflammation of the brain to coma. For the survivors, it’s too early to say if their brief time with the virus could lead to neurological problems later on in life. Instead, Haeman Jang from St Jude’s Children’s Research Hospital turned to mice for answers.
He clearly showed that the H5N1 virus can infect mouse neurons within a few days, where it causes certain proteins to gather in the sorts of clumps that are so strongly associated with neurodegenerative disease. It kills off important cells, triggers symptoms reminiscent of Parkinson’s like tremors, and even stimulates an over-the-top immune response that lasted for months after the original infection was cleared.
Jang thinks that this long-lasting immune response may be how the virus leads to a higher risk of chronic diseases long after it has left its host. It’s a hit-and-run strategy, where the initial infection paves the way for something else to come along later on in life and make a “second hit”. According to this model, the flu virus doesn’t directly cause Parkinson’s or related diseases, but it primes the neurons for other things that do. This could also explain why scientists have been unable to detect influenza RNA in Parkinson’s patients.