Neuroinflammation, activation of innate immune components of the nervous system followed by an adaptive immune response, is observed in most leukodystrophies and coincides with white matter pathology, disease progression, and morbidity. Despite this, there is a major gap in our knowledge of the contribution of the immune system to disease phenotype. Inflammation in Krabbe's disease has been considered a secondary effect, resulting from cell-autonomous oligodendroglial cell death or myelin loss resulting from psychosine accumulation. However, recent studies have shown immune activation preceding clinical symptoms and white matter pathology. Moreover, the therapeutic effect underlying hematopoietic stem cell transplantation, the only treatment for Krabbe's disease, has been demonstrated to occur via immunomodulation. This Review highlights recent advances in elaboration of the immune cascade involved in Krabbe's disease. Mechanistic insight into the inflammatory pathways participating in myelin and axon loss or preservation may lead to novel therapeutic approaches for this disorder. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.
Keywords: DOID:10587; GALC; NIFCELL:NIFEXT_170; PR:0000007811; RRID:IMSR_JAX:000845; RRID:IMSR_JAX:003613; globoid cell leukodystrophy; microglia; twi-5J; twitcher.
© 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.