To make a definitive diagnosis of Alzheimer’s, doctors rely on the appearance in the brain of amyloid beta plaques – an accumulation of said protein – and neurofibrillary tangles – which are mainly composed of tau protein, together with the manifestation of symptoms of dementia, which is why plaques are considered to be the main cause of Alzheimer’s. However, a new study suggests that impaired autophagy, or the cells’ ability to clean themselves, is a new probable cause of this neurodegenerative disease.
The research, whose results have been published in the Journal of Proteome Research, has been carried out by scientists from the University of California Riverside (UC Riverside), who focused on carefully examining the tau protein to better understand the mechanism by which the plates and tangles. “Approximately 20% of people have the plaques, but there are no signs of dementia,” said Ryan Julian, a professor of chemistry at UCR, who adds that “this makes it seem that the plaques themselves are not the cause. ”.
The study focused on the various forms that a single molecule can take, called isomers. “An isomer is the same molecule with a different three-dimensional orientation than the original,” Julian explained. “A common example would be hands. The hands are isomers of each other, mirror images but not exact copies. Isomers can be really right-handed.” According to the expert, the amino acids that make up proteins can be right-handed or left-handed isomers and, in general, all the amino acids in the proteins of living beings are left-handed.
Induce cellular autophagy to prevent Alzheimer’s
The researchers found a key, albeit difficult to detect, difference in the form of tau, which allowed them to distinguish individuals who showed outward signs of dementia from those who did not. They scanned all the proteins in donated brain samples and found that those with buildup in the brain but who had not shown signs of dementia had normal tau, while the form of tau was from different hands in those who developed plaques or tangles. along with dementia.
“About 20% of people have the plaques, but there are no signs of dementia,” and “this makes it appear that the plaques themselves are not the cause of Alzheimer’s.”
Most proteins in the body have a half-life of less than 48 hours, but if the protein is kept too long, certain amino acids can transform into the other hand isomer. Julian explains with an example: “If you try to put a right-handed glove on your left hand, it doesn’t work very well. It’s a similar problem in biology; the molecules don’t work the way they’re supposed to after a while because a left-handed glove can actually become a right-handed glove that doesn’t fit.”
Aging influences the process of removing worn or defective proteins from cells – known as autophagy – which slows down in people over 65 years of age. The reasons for this are unknown, but drugs that enhance autophagy are currently being tested, some of which are already approved to treat cardiovascular diseases, among others.
It is possible to induce autophagy with physical exercise and fasting, because when a person’s diet does not provide enough protein to the cells, they compensate for the lack by recycling the proteins that are already present in the cells. These strategies and treatment with certain drugs could help prevent Alzheimer’s. In Julian’s opinion: “If a slowdown in autophagy is the underlying cause, things that increase it should have the opposite beneficial effect.”
.
