Although a link has been established between chronic inflammation and neurodegenerative diseases, there have been many open questions regarding how cellular senescence, a process whereby cells that stop dividing under stress spew out a mix of inflammatory proteins, affects these pathologies. Publishing in PLOS ONE, researchers at the Buck Institute report that senescence in astrocytes, the most abundant cell type in the brain, leads to damaging "excitotoxicity" in cortical neurons that are involved in memory.
This research, led by research scientist Chandani Limbad, PhD, found that cellular senescence in astrocytes downregulates the glutamate transporters, which are vital for glutamate homeostasis in the brain. Glutamate is one of the most important neurotransmitters in the brain; an excess of it causes neurons to repeatedly fire leading to their eventual death. Memantine, an FDA-approved drug for Alzheimer's disease, reduces glutamate toxicity in patients suffering from moderate to severe disease for up to a year, but evidence that the drug might slow pathology is weak.
This study gets to the underlying mechanisms that drive the toxicity. We have identified targets that may be of more use in drug development." Judith Campisi, PhD, senior author, Buck professor
Cellular senescence is one of the hottest topics in research on aging. Success in the Campisi lab and others around the world has given rise to companies and research projects aimed at developing either senolytics, drugs that clear senescent cells, or senomorphics, drugs that suppress the senescence-associated inflammation. Earlier work in the Campisi lab in collaboration with the Buck Institute's Andersen lab showed that clearing senescent cells prevented Parkinson's in a mouse model of the disease. Related Stories
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