In Mad cow disease, misfolded proteins called prions drill holes in the brain, eventually destroy. Hereditary prion diseases, which are rare and passed through families, do the same. But it has long been a puzzle why prion attack neurons than other cell types, and how they do their damage. In a new study, the researchers suggest that prions deplete a misunderstood protein that normally keeps nerve cells healthy. The theory has some way to go before it can be proven, but researchers are intrigued by this potential new twist on a mysterious disease
Prions are a defective version of a protein called PrP healthy. when it misfolds, the results are disastrous. Yet researchers do not know exactly why. One argument suggests that, while health PrP is normally located on the surface of the cell, the lost and pray are found in the cytosol, the fluid found inside cells, destroying them in some way.
The new study bolsters the theory. The first signs came in an article published in 03. In this work, the researchers reported that mice lacking an obscure protein, Mahogunin, has suffered some form of neurodegeneration much like prion diseases. Biologists phones Ramanujan Hegde and Oishee Chakrabarti of the National Institute of Child Health and Human Development in Bethesda, Maryland, decided to probe deeper into the Mahogunin connection.
The team tested whether artificial prion proteins, constructed to resemble real prion, interact with Mahogunin. They did - but because prions are sticky and adhere to almost everything, it was not sufficient evidence. Thus, the researchers showed that this interaction has caused problems for Mahogunin in living cells: Adding artificial prion depleted levels of Mahogunin but when prions were prevented from entering the cytosol, the Mahogunin levels remained normal. Finally, mice with a mutation in the gene PrP , which develop prion disease, also lost Mahogunin in parts of their brain, the duo reports today Cell .
Although there is still no evidence that Mahogunin plays a role in the infectious prions to diseases such as mad cow disease, the theory is reasonable for hereditary cases, which more closely resemble this which is seen in the mice used here, says Adriano Aguzzi, a neuropathologist at the University of Zurich in Switzerland. "At first glance, it is plausible," agrees Neil Cashman, a neuroscientist at the University of British Columbia in Vancouver, Canada, said that the theory needs to be tested further. One question, Cashman said, is knowing Mahogunin if the mechanism is consistent with other theories that attempt to explain the toxicity of prion, such as those attributed to the defective cell signaling.
the authors agree that there are many unanswered questions. one is why a deficit of Mahogunin detrimental to a cell. Hegde is also interested in whether prions exhaust other cells and molecules.
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