Necroptosis strikes again
Direct evidence of necroptosis in Alzheimer's
Adding to the list of necroptosis-related pathologies, a group from Arizona State University has shown the cell death pathway is activated in Alzheimer’s disease. The data, published last month in Nature Neuroscience, identify potential targets in the pathway and open the door to investigation of whether blocking necroptosis can complement therapeutic strategies aimed at upstream cytotoxic insults.
Necroptosis is a form of programmed cell death that is associated with inflammation and characterized by cell swelling and membrane rupture, in contrast to the DNA fragmentation and cell shrinkage that marks apoptosis. Necroptosis is driven by the activation and phosphorylation of three central signaling proteins: RIPK1, RIPK3 and MLKL.
While DNA fragmentation- and apoptosis-related caspases have been seen in brains from AD patients, the more proximal signs of apoptotic death such as apoptotic bodies and chromatin condensation have not, which suggests another death pathway may be associated with the disease.
Salvatore Oddo, who led the study, told BioCentury that a key goal in the field is to find links between the observed macro changes and cellular markers that could reveal the mechanism.
“The brain is physically smaller in Alzheimer's and that’s well established. The point of this paper was to understand how all these neurons are dying," Oddo told BioCentury. Oddo is an