There may be a single cause behind the molecular chaos that triggers Alzheimer's: the formation of granules of RNA and proteins in nerve cells, a process that usually occurs in response to stress conditions but can sometimes become chronic, causing a blockage of transport between the nucleus and the cytoplasm that sends neurons into a tailspin.
Proposing this new unifying theory, which for the first time seems to be able to explain all the various molecular alterations typical of the disease, are researchers from Arizona State University, in an article published in the journal Alzheimer's & Dementia.
Their work, the result of a systematic review of literature and biomathematical analyses of existing databases, offers a unique framework for fitting together decades of fragmented research on Alzheimer's that has focused on different aspects of the disease, such as amyloid plaques, tau protein tangles, inflammation, and various cellular dysfunctions.
Researchers led by Paul Coleman argue that all these changes may be traced to a single cause: so-called stress granules, clumps of RNA and proteins that temporarily form in response to cellular stress triggered by, for example, genetic mutations, inflammation, exposure to pesticides, viruses, and air pollution. These granules pause nonessential processes while the cell recovers, and dissolve once the stress subsides. In Alzheimer's disease, however, the granules persist abnormally and become chronic, eventually trapping vital molecules and impeding their movement to and from the cell nucleus. This disruption in transport blocks the production of essential proteins and alters the molecular switches that control the activity of more than a thousand genes, resulting in a cascade of the various clinical manifestations of Alzheimer's.
These changes occur very early, even before the typical signs of the disease such as amyloid plaques or tau tangles appear. Identifying and addressing the formation of pathological stress granules in the early stages, therefore, could significantly halt or delay the onset of symptoms.
(Online Union)
