La leucoencefalopatía relacionada con el receptor CSF-1 (CRL) es una enfermedad neurodegenerativa rara que provoca demencia y deterioro motor, causada por mutaciones con pérdida de función en el gen CSF1R, fundamental para el desarrollo y la función de las células inmunitarias del cerebro conocidas como microglía. Utilizando un modelo de ratón de CRL que ellos mismos desarrollaron, E. Richard Stanley, Ph.D., Violeta Chitu, Ph.D., y sus colegas del Albert Einstein College of Medicine y otros centros estudiaron los cambios tempranos en la microglía antes de que aparecieran los síntomas.

As described in a study published February 26 in the Revista de investigación clínica, reduced signaling through the CSF-1 receptor disrupts how microglia regulate the distribution of essential metal ions such as zinc, copper, and iron in the brain. CRL microglia begin to abnormally accumulate and effectively “trap” these metals, depriving other brain cells, such as neurons and endothelial (blood vessel) cells, of the ions they need to function properly. This imbalance—marked by excess metal buildup in microglia and reduced availability to other cells—occurs on the background of decreased levels of metallothioneins, proteins that normally regulate metal distribution and protect cells from oxidative damage. Even presymptomatically, these changes trigger stress responses and early dysfunction in neurons, oligodendrocytes (cells that help insulate nerve fibers), and endothelial cells. Over time, these disruptions contribute to neurodegeneration. Importantly, restoring metallothionein levels in mice corrected metal imbalances, reduced cellular stress, and prevented behavioral symptoms. The findings suggest potential strategies for preventing CRL and possibly other neurodegenerative disorders.

El Dr. Stanley es profesor emérito de biología del desarrollo y molecular . El Dr. Chitu, primer autor, es profesor investigador de biología del desarrollo y molecular.