Small particles of prion protein are much more efficiently infectious than large ones, yet there is also a lower size limit below which infectivity is lost, scientists reported on Wednesday.

Prions are apparently malformed proteins blamed for deadly brain diseases, such as the mad cow disease in cattle and Creutzfeldt-Jakob disease in humans. Prion diseases are also known as transmissible spongiform encephalopathies (TSEs) because the prions create holes in the brain, giving it a sponge-like appearance.

In a latest study, researchers from US National Institute of Allergy and Infectious Diseases (NIAID) found the link between the proteins' size and their infectivity. Their findings appear in the Sept. 8 issue of the journal Nature.

The most infectious prions are significantly smaller than the large thread-like deposits of protein molecules readily seen in the diseased brains of infected individuals.

Scientists have known that infectious prions range widely in size, but now for the first time the researchers ranked them according to their infective efficiency, and their findings have placed new limits on the size of the smallest prion.

Prions appear to be crystal-like clusters of protein molecules that can grab normal, dissolved protein molecules and convert them to a solid, crystal-like state, said Byron Caughey, senior researcher at NIAID's Rocky Mountain Laboratory.

"Although large prion particles can do this, and are infectious, you can infect many more individuals, or cause much more rapid disease in a single individual, with an equivalent weight of small prion particles," said Caughey.

"But our findings also suggest that if the protein cluster is smaller than a certain minimum size, it becomes unstable and loses its infectious properties."

Normal protein molecules found in many animals do not cause harm, but they can become lethal and destroy the brain when they refold and gather into precisely ordered clusters.

"As you increase particle size steadily from single molecules to particles containing thousands of molecules, there's a sudden jump in infectivity once you get to the minimum infectious particle size (at least six molecules per particle)," he explained.

"Soon the most infectious particles appear (equivalent in weight to 14 to 28 molecules per particle), followed by larger thread-like particles that are still infectious, but less so, per unit of protein."

These findings are consistent with evidences in many other neurological protein aggregation diseases, that small, misfolded clusters are more damaging than large clusters.

Thus the treatments designed to break apart large accumulations of prions in the brain might do more harm than good by releasing the most infectious prion particles, resulting in more widespread damage, the researchers noted.

"Large deposits, or plaques, could be an attempt by the brain to detoxify the infectivity, to protect the brain," Caughey said.

Source: Xinhua