LA JOLLA, June 5 — Researchers at Scripps Research have made a significant discovery in understanding the molecular mechanism behind the chronic inflammation in Alzheimer’s disease, a finding that could potentially lead to new treatments for the condition. At the center of this breakthrough is a protein called STING, which normally serves as an early-warning system against infection, but in Alzheimer’s, undergoes a chemical change that transforms it into a hyperactive form, continuously pumping out inflammatory signals.
The protein clumps associated with Alzheimer’s, such as amyloid-beta and alpha-synuclein, can trigger this change in STING, sparking a self-perpetuating cycle of inflammation that destroys synaptic connections between neurons, with factors such as aging, air pollution and even wildfire smoke fueling it by raising nitric oxide in the brain.
The researchers, led by neurologist Stuart Lipton, found that blocking the modification in mice significantly reduced neuroinflammation and protected those synaptic connections, whose loss correlates with cognitive decline, offering a promising new avenue for treatment. What’s key here is that targeting the specific modification on the STING protein, at a single building block called cysteine 148, quiets only the harmful overactivation of the immune system, leaving normal immune defenses intact, a more precise approach than broad anti-inflammatory drugs.
According to the researchers, this discovery could open up a new path forward in treating Alzheimer’s, as most amyloid-focused trials have been disappointing, and this shift toward addressing neuroinflammation could lead to more effective treatments, with the team already working on developing small molecules to block the harmful modification.
While the work is still preclinical, the potential for this new approach to make a significant impact on the lives of those affected by Alzheimer’s is undeniable, and as researchers continue to develop and test new treatments, there is renewed hope for finding effective ways to combat this devastating disease.
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