USC researchers identify compounds targeting Alzheimer’s brain inflammation

Scientists at the University of Southern California have found experimental compounds that may reduce harmful brain inflammation associated with Alzheimer’s disease. The work focuses on the enzyme cPLA2 and people who carry the high-risk APOE4 gene.

Researchers at the University of Southern California identified compounds that selectively inhibit cPLA2, an enzyme tied to inflammation in the brain. The findings were published in the journal npj Drug Discovery in 2026. The team linked higher cPLA2 activity to greater Alzheimer’s risk among APOE4 carriers, though the enzyme also supports normal brain function.

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Microscopic illustration of protective microglia clearing amyloid plaques in an Alzheimer's brain model due to the OLE molecule
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Study identifies OLE molecule that shifts microglia into a more protective state in Alzheimer’s models

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Researchers in Spain and Switzerland report that an experimental molecule called OLE helped restore protective behavior in the brain’s immune cells in animal models of Alzheimer’s disease, reducing amyloid-related pathology and improving performance on memory and movement tests.

Researchers at the Indiana University School of Medicine have identified the enzyme IDOL as a potential new target for treating Alzheimer's disease. Laboratory studies showed that removing the enzyme from neurons reduced amyloid plaques and improved brain cell communication.

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A major analysis of genetic data has linked 127 gene locations to Alzheimer’s disease, including 48 previously unidentified ones. Researchers also flagged several genes as promising drug targets and highlighted changes in immune and nerve cells.

Researchers at the University of Kentucky report that overactive microglia—immune cells in the brain—can drive sleep loss in mice with amyloid plaques. In the study, temporarily depleting most microglia restored more than two hours of sleep per day, even though plaque levels did not change.

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A major Cochrane review of 17 clinical trials involving over 20,000 participants has concluded that drugs targeting amyloid beta in the brain provide no meaningful benefits for patients with mild cognitive impairment or early Alzheimer’s. These treatments also raise the risk of brain swelling and bleeding. Researchers urge a shift to alternative pathways for future treatments.

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