Prions Similar To The Proteins That Cause Mad-Cow Disease May Be Essential In Brain Development

There aren't many diseases that are scarier than Creuzfeldt-Jakob disease. Like another disease that is spread among brain-eating cannibals in New Guinea called kuru, Creuzfeldt-Jakob disease causes progressive loss of brain functions that slowly destroy mobility and personality and inevitably result in death over a period of 6 to 24 months.

It's likely that early observations of conditions like kuru and Creuzfeldt-Jakob disease gave rise to the legends of zombies. Like the fictional zombie-ism, these prion diseases can be spread from person to person by eating brains. For the real life diseases, there is no known cure, and the causative agent is known to be a prion.

What's a Prion?

A prion is a protein. Smaller even than a virus, prions are essentially indestructible. They are undetectible by the immune system. Drugs have no effect on them. They can't be irradiated. They can't be dissolved. They exist indefinitely anywhere they land, for instance, on a surgical tool, or a cannibal's fork, on metal surfaces, in the ground, or in the air. It's impossible to clean them off surgical instruments.

Fortunately, prions essentially never appear spontaneously. Either a genetic mutation programs the brain to produce prions, or a prion introduced into the body (typically in a surgical accident, or by cannibalism of an infected person's brain) attracts circulating amino acids and creates "dimers" to make multiple copies of itself. Literally trillions, quadrillions, and quintillions of prions may emerge after infection with a single particle.

In the brain, infectious prions interact with long strands of brain tissue known as fibrils to cause mats of dysfunctional, disruptive proteins known as tangles. These tangles stop the transmission of signals from neuron to neuron in the brain and eventually cause complete disruption of the brain and death.

Prion Diseases Are Deadly

The health conditions caused by prions are untreatable and death is inevitable. There is no known cure for any of the prion diseases of humans or any other animal. Prions transmitted from cow brains to humans cause Creuzfeldt-Jakob or mad-cow disease, prions transmitted from human brains to humans cause the disease of cannibals known as kuru, and there are also prion diseases of deer (which can be contracted by hunters who handle or eat them), ostriches, elk, sheep, goats, moose, mice, cats, nyalas, oryx, and greater kudus.

There are also similarly deadly genetic prion diseases (diseases in which the brain makes its own disease-causing prions) in people such as fatal familial insomnia and a brain-wasting Gerstmann–Sträussler–Scheinker syndrome. But some of the latest research suggests that prions aren't always bad.

Prions Potentially Play A Role In Brain Development

Prions, scientists have learned over the last 20 years, don't always cause disease. Prions have two different forms. There is a malformed, literally twisted, infectious form of a prion that attaches to enzymes that allow it to make vast numbers of copies of itself. And there is also a non-infectious, "unfolded" version of prion that exists in every cell in the body.

The non-infectious prion, known as a cellular prion protein or PrPC, seems to play an important role in the brain. It helps to make the proteins that form a protective, myelin sheath around neurons. PrPC is especially abundant in the neurons of growing brains, where it apparently helps neurons pass messages to each other.

A Clue to a Useful Role for Prions from Laboratory Research

Neuroscientist Enrico Cherubini of the International School for Advanced Studies in Trieste, Italy studied the brains of mice specially bred to lack the gene for making cellular prion protein. Looking at slices of the hippocampus, the region of the brain most involved in forming new memories, they used electrodes to provide bursts of electricity analogous to the firings of neurons involved in learning.

In the brains of healthy mice that had cellular prion protein, stimulating the hippocampus helped neurons form connections with each other. These connections may form a kind of "engram" that stores memories of experience in a form that the brain can retrieve.

In the brains of mice bred to lack cellular prion protein, however, stimulating the hippocampus had the opposite effect. Instead of forming new connections, the prion-free neurons lost connections, and their activity became depressed. The presence of prions, Cherubini and his collaborators believe, may be essential to the growth of the brain and the learning of basic skills in mice and in people.

Prions Promote Plasticity

Further experiments revealed that prion proteins help the brain to become "plastic," able to rewire itself when neurons are damaged or destroyed. Prions may be especially important in helping the brain store and retrieve visual memories, and in maintaining eye-hand (or in the case of laboratory mice, eye-paw, coordination).

Everything about prions, it turns out, probably is not bad. And if you are worried about catching mad-cow disease, don't. There have been only a few hundred cases in Europe and fewer than 20 in North America and Asia. Even better, the only zombies you'll ever have to concern yourself with are those you see on TV and in the movies.