Loss of ATP13A2 function leads to lysosomal polyamine sequestration, depleting cytosolic polyamines in astrocytes. This triggers compensatory polyamine biosynthesis, diverting SAM from DNA methylation and promoting neuroinflammation.
Polyamines are crucial for brain function. ATP13A4 is the main polyamine transporter in astrocytes, impacting astrocyte morphology, synapse formation, and neurodevelopment. Mutations in ATP13A4 are linked to neurodevelopmental disorders.
The protocol describes in detail how to induce GCase loss of function in mice using CBE treatment. Mice exhibit severe motor symptoms accompanied by neuroinflammation after four weeks of daily CBE injections using this protocol.
