Brain pathology in Niemann Pick disease type A: insights from the acid sphingomyelinase knockout mice

J Neurochem. 2011 Mar;116(5):779-88. doi: 10.1111/j.1471-4159.2010.07034.x. Epub 2011 Jan 7.


Severe neurological involvement characterizes Niemann Pick disease (NPD) type A, an inherited disorder caused by loss of function mutations in the gene encoding acid sphingomyelinase (ASM). Mice lacking ASM, which mimic NPD type A, have provided important insights into the aberrant brain phenotypes induced by ASM deficiency. For example, lipid alterations, including the accumulation of sphingolipids, affect the membranes of different subcellular compartments of neurons and glial cells, leading to anomalies in signalling pathways, neuronal polarization, calcium homeostasis, synaptic plasticity, myelin production or immune response. These findings contribute to our understanding of the overall role of sphingolipids and their metabolic enzymes in brain physiology, and pave the way to design and test new therapeutic strategies for type A NPD and other neurodegenerative disorders. Some of these have already been tested in mice lacking ASM with promising results.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / pathology*
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Knockout
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • Niemann-Pick Disease, Type A / genetics*
  • Niemann-Pick Disease, Type A / pathology*
  • Sphingomyelin Phosphodiesterase / deficiency*


  • acid sphingomyelinase-1
  • Sphingomyelin Phosphodiesterase