Who’d think that clogging up the garbage disposal would clean up the kitchen?
Yet, as a new study by molecular and cellular physiologist Tom Sudhof, MD, and his Stanford colleagues, just published online in Science Translational Medicine, suggests just that. As I wrote in my release about the study:
…blocking the activity of cells’ in-house garbage disposals — known in the biology business as proteasomes — …both delayed the onset of symptoms in laboratory mice that are highly prone to neurodegeneration and significantly increased their longevity.
Proteasomes are cell components that destroy banged-up proteins. Not just nerve cells but virtually all cells in creatures ranging from yeast to humans contain multitudes of these tiny tubular machines, which suck the defective proteins into their holes and chew them into smithereens.
You might expect that when proteins get so bent out of shape that they can no longer do their job, we’d be better off without them. So, a lot of scientific effort and corporate expense have been devoted to efforts to treat neurodegenerative disorders such as Alzheimer’s disease by ridding patients’ bodies (and therefore, it is hoped, their brains) of faulty proteins.
But Sudhof thinks this common-sense conclusion may need to be revisited. In a separate experiment described in the same study, his team also examined brain tissue from Alzheimer’s and Parkinson’s patients – two of a growing number of diseases for which the clumping together of misfolded proteins is believed to be at least partially culpable – and observed signs of the same deficits in healthy biochemical activity that inhbiting proteasomes had restored in the experimental mice.
Sudhof suspects that shoving the pharmacological equivalent of a spoon into a cell’s proteasomes, which causes the buildup of damaged proteins, results in a fair number of those proteins – either randomly or with the assistance of physical-therapist molecules called “chaperones” – reverting back to the correct shape, restoring key biochemical processes without which nerve cells die.
Photo by Suzie Tremmel