New Delhi: Alzheimer’s disease is one of the medical community’s biggest unsolved challenges. Now, a new atlas of the brain’s microproteins might help scientists figure out how to battle the degenerative neurological disorder.
The findings were published in Nature Aging on 14 September by researchers at the Salk Institute, an independent non-profit scientific research organisation in California.
“We still do not fully understand the molecular mechanisms of healthy ageing, and that is especially true for microproteins, which have been inadvertently overlooked for decades. Our atlas allows scientists to systematically investigate microproteins in ageing and neurodegeneration, which should bring us closer to understanding and tackling diseases like Alzheimer’s or Parkinson’s,” said senior author Alan Saghatelian in a statement.
The team used 480 samples of the human frontal cortex, both with and without Alzheimer’s disease and found 1,067 new microproteins. They even found a link between one of the microproteins and a type of immune cell dysfunction linked to Alzheimer’s disease.
What makes microproteins so important?
Every human cell uses the same DNA code to function, but each cell refers to it differently and chooses the type of proteins it produces. The proteins a cell produces determine its identity and, therefore, identifying these proteins becomes a key to understanding how a cell functions and why it might act differently.
In the case of Alzheimer’s, too, scientists are trying to understand the proteins that are essential to brain function and how they can potentially be targeted to treat the disease. While they already do have a good understanding of proteins, microproteins are far less studied.
“Every coach has a playbook, and you want as many plays as possible to win the game. For scientists, the game is trying to understand the disease, and the plays are the proteins and microproteins that may or may not be involved in that disease,” said Brendan Miller, a postdoctoral researcher at Saghatelian’s lab.
The study further found that the brain of an Alzheimer’s patient expressed microproteins differently compared to a healthy brain. While some microproteins were expressed more and others less, cells affected by Alzheimer’s expressed more proteins overall.
Researchers also studied one particular type of brain cell in the frontal cortex, the microglia, which often turns dysfunctional with age or in cases of neurodegenerative diseases like Alzheimer’s. They found that when they disabled the microprotein-making gene in microglia, the cell became dysfunctional.
“There is sometimes an assumption that we know everything about our genome, and we know all the genes our cells can make—that’s just not true. What we know is constantly expanding, and this atlas makes it that much easier to study microproteins in life science research,” Saghatelian added.
(Edited by Insha Jalil Waziri)