BACKGROUND
UCLA scientists discovered that a cell type long implicated in brain diseases is remarkably malleable and shows responses in a mouse model that suggest potential targets for drugs for Huntington's disease. Astrocytes, named after their star-like shape, tile the central nervous system yet the molecular mechanisms by which they contribute to neurological diseases remain poorly understood.
FINDINGS
Researchers discovered three distinct findings. First, astrocytes in a brain region called the striatum mount context-specific molecular responses at the level of genes, pathways and molecular regulators. Second, the team identified astrocyte pathways in Huntington's disease that were reciprocally altered by the activation of a receptor on the striatal astrocyte.
Third, they showed that stimulating a striatal astrocyte pathway improved its signaling, thereby correcting several symptoms related to Huntington's disease.
IMPLICATIONS
A cure for Huntington's disease would entail tediously removing the mutant Huntington protein from all cells. Alternately, the UCLA data indicate that harnessing astrocyte mechanisms in a live mouse produces beneficial effects at the molecular, cellular and behavioral levels to improve Huntington's-associated symptoms. Neuroscientists could exploit this approach as a novel therapeutic strategy in Huntington's and other brain disorders.
AUTHORS
Baljit Khakh, PhD, professor of physiology and neurobiology at the David Geffen School of Medicine at UCLA, is available for interviews. Xinzhu Yu and Jun Nagai were the study's joint first authors.
FUNDING
Grants from the National Institute of Neurological Diseases and Stroke, the Paul G. Allen Frontiers Group, the Ressler Family Foundation and CHDI Foundation supported the research.
PUBLICATION
The journal Neuron published the findings.
