From Lab to Life: Alzheimer’s & Brain Trash

New research at my university, Technion, may reveal a key finding in solving the riddle of Alzheimer’s: Our brains are not disposing of their trash properly. A research group led by Professor Michael Glickman, dean of the Technion’s Faculty of Biology (and a post-doc A.R. Wagh)  has discovered that a mechanism responsible for breaking down toxic proteins, and known to be involved in the development of Alzheimer’s disease, may actually spread these proteins to neighboring cells, thereby promoting the progression of the disease in the brain.

“In their article, they describe how brain cells deal with UBB+1, a defective and toxic variant of the protein ubiquitin.   The ubiquitin system is essential for breaking down damaged and dangerous proteins. Ubiquitin helps the body eliminate such proteins. The problem arises when ubiquitin mutates into UBB+1. Instead of protecting the cell, UBB+1 harms it, forming protein aggregates associated with the development of Alzheimer’s disease. In brain cells, this damage is particularly severe because neurons do not divide or regenerate – once a neuron dies, it cannot be replaced.” In other words, neurons protect themselves by dumping the trash – but it can accumulate and gum up our brains.

Technion professors Avram Hershko and Aaron Ciechanover won a Nobel Prize in 2004 for their discovery of ubiquitin, which “mediates protein degradation” and tosses them into the trash bin when they no longer function properly.

This discovery by Glickman and Wagh could ultimately help researchers find ways to combat UBB+1, and prevent the plaque that clogs our brains and leads to dementia.

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Wagh, A. R., & Glickman, M. H. (2025). Molecular mechanisms underlying p62-dependent secretion of the Alzheimer-associated ubiquitin variant UBB+ 1. Proceedings of the National Academy of Sciences, 122(50), e2504528122.