IT IS a redemption of sorts. The much maligned prion proteins that cause mad cow disease and its human counterpart, variant Creutzfeldt-Jakob disease (vCJD), also play a key role preventing the progress of Alzheimer鈥檚. In a separate development, a potential new treatment for vCJD has been developed in Japan.
鈥淓veryone assumes the prion protein is something bad,鈥� says Nigel Hooper of the University of Leeds, UK, who headed the team that has discovered the link to Alzheimer鈥檚. 鈥淣ow it appears it鈥檚 there for a reason.鈥�
Prions are found in all brain cells. Trouble begins when they into abnormal versions of the protein. These can then trigger normal proteins to also misfold, producing a chain reaction that clogs the brain with abnormal proteins and so causing diseases such as vCJD.
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Brains of patients with Alzheimer鈥檚 disease clog up too, but with plaques made from a different protein called amyloid beta peptide. Now Hooper鈥檚 team says it has found a crucial and unexpected link between prions and Alzheimer鈥檚 (Proceedings of the National Academy of Sciences, ).
In tests on human brain cells engineered to make more normal prions than usual, Hooper found that the cells secreted far less amyloid beta peptide than they would ordinarily. The reverse happened in cells engineered to make too few normal prions. Mice engineered to create no normal prions at all in their brains also produced far higher amounts than normal of the amyloid beta protein that causes Alzheimer鈥檚. The researchers demonstrated that the prion proteins blocked beta-secretase, an enzyme vital for making amyloid beta peptide. In other words, the prion protein protects the brain from build-up of the plaque that causes Alzheimer鈥檚 disease.
Hooper says this tallies with the results of post-mortems on people who died from Alzheimer鈥檚 disease around the age of 40. Genetic analysis showed they had mutations in the prion gene PrP, suggesting they lacked this protection.
Glenn Millhauser of the University of California, Santa Cruz, says that the protective effects of the prion protein have been spotted before, but the mechanism was unknown. 鈥淲hat鈥檚 distinct here is a regulatory role whereby the prion protein inhibits production of amyloid beta peptide from its precursor protein,鈥� says Millhauser.
Hooper says that prions probably have other roles too, such as maintaining stem cells. However, the discovery that they help protect the brain might lead to new drugs that mimic their function to treat Alzheimer鈥檚.
Meanwhile Kazuo Kuwata and colleagues at Gifu University in Japan have developed a molecule called GN8 that has potential to prevent vCJD by binding to the normal prion protein and preventing it misfolding into the abnormal form that causes disease. Initial tests show the chemical prolongs the survival of mice deliberately infected with prion disease (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0702671104).
