Protein wangles recruits to do dirty work

STANFORD (US) — A mutant misfolded protein is successful at causing neurodegenerative diseases by moving from cell to cell, corrupting normal proteins into joining its crusade.

The proteins’ stealthy ability could explain the way Huntington’s disease spreads through the brain after starting in a specific region. Similar mechanisms may be involved in the progress of Parkinson’s and Alzheimer’s through the brain as well.

Knowing that this protein spends part of its time outside cells opens up the possibility for new targeted drug therapies that could prevent or at least block progression of disease, says Ron Kopito, professor of biology at Stanford University.

Kopito discussed how misfolded proteins get across a cell’s membrane and into its cytoplasm, where they can interact with normal proteins at the recent annual meeting of the American Association for the Advancement of Science in Washington, D.C.

Not all bad

Not all misfolded proteins are bad, Kopito says.  Over the past 20 years, researchers have found that as much as 30 percent of proteins never fold into stable structures. And even ordered proteins appear to have some disordered parts.

Disordered proteins are important for normal cellular functions. Unlike regular proteins, they interact with only one partner at a time, but are much more dynamic, making them ideal for a lot of the standard communication that happens within a cell for its normal functioning.

The question of how cells know which proteins need to be propely folded has implications for people who develop neurodegenerative diseases, all of which appear to be age-related. The body appears to stop making protective mechanisms as it ages, Kopito says.

For example, the mutant protein associated with Huntington’s disease, which starts in one area of the brain and spreads to the rest of it, can leave one cell and enter another one, stirring up trouble in each new cell as it progresses down the line.

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