– Neurology research can include information involving brain research, neurological disorders, medicine, brain cancer, peripheral nervous systems, central nervous systems, nerve damage, brain tumors, seizures, neurosurgery, electrophysiology, BMI, brain injuries, paralysis and spinal cord treatments.The discovery of how to shift damaged brain cells from a diseased state into a healthy one presents a potential new path to treating Alzheimer’s and other forms of dementia, according to a new study from researchers at UC San Francisco.The research focuses on microglia, cells that stabilize the brain by clearing out damaged neurons and the protein plaques often associated with dementia and other brain diseases. .These cells are understudied, despite the fact that changes in them are known to play a significant role Alzheimer’s and other brain diseases, said Martin Kampmann, PhD, senior author on the study, which appears Aug.
Ordinary immune cells can’t cross the blood-brain barrier, so it’s the task of healthy microglia to clear out waste and toxins, keeping neurons functioning at their best.Over the past five years or so, many studies have observed and profiled these varying microglial states but haven’t been able to characterize the genetics behind them. .Kampmann and his team wanted to identify exactly which genes are involved in specific states of microglial activity, and how each of those states are regulated.To overcome this, Kampmann’s team coaxed stem cells donated by human volunteers to become microglia and confirmed that these cells function like their ordinary human counterparts.
The team then developed a new platform that combines a form of CRISPR, which enables researchers to turn individual genes on and off—and which Kampmann had a significant hand in developing—with readouts of data that indicate functions and states of individual microglia cells.And because the scientists had determined which genes control those activities, they were able to reset the genes and flip the diseased cell to a healthy state.Armed with this new technique, Kampmann plans to investigate how to control the relevant states of microglia, by targeting the cells with existing pharmaceutical molecules and testing them in preclinical models.
“A CRISPRi/a platform in human iPSC-derived microglia uncovers regulators of disease states” by Martin Kampmann et alA CRISPRi/a platform in human iPSC-derived microglia uncovers regulators of disease statesA screen with single-cell RNA sequencing as the readout revealed that these microglia adopt a spectrum of states mirroring those observed in human brains and identified regulators of these statesThus, our platform can systematically uncover regulators of microglial states, enabling their functional characterization and therapeutic targeting
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