TREATING NEURODEGENERATIVE DISEASE

摘要

As described herein, lactosylceramide (LacCer) levels are up-regulated in the CNS during chronic experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). LacCer acts in an autocrine manner to trigger transcriptional programs that promote the recruitment and activation of CNS infiltrating monocytes and microglia, and neurodegeneration. In addition, increased B4GALT6 expression and LacCer levels were detected in CNS MS lesions in human patients. Finally, the inhibition of LacCer synthesis suppressed local CNS innate immunity and neurodegeneration in EAE, and interfered with the activation of human astrocytes in vitro. Thus, B4GALT6 is a therapeutic target for MS and other neuroinflammatory disorders.