Purpose of review: Progressive neurological deterioration is the ultimate cause of premature death in Niemann-Pick type C disease. Yet it remains unknown why a defect in basic cellular lipid homeostasis would lead to such profound neurological dysfunction and degeneration. The established belief that the central nervous system disorder of Niemann-Pick type C disease is secondary to lipid accumulation has led to a deficiency of research and information on the neurological manifestation of the disease. Lipid and vesicular trafficking have been studied extensively in non-neuronal cells such as fibroblasts and significant advances have been summarized in excellent reviews. The purpose of the present review is to consolidate the findings on brain lipid metabolism and Niemann-Pick type C disease neuropathology, so as to generate a current picture of the central nervous system disease, and emphasize potential aspects for future research.
Recent findings: Some key findings in the last couple of years have brought the neurological features of Niemann-Pick type C disease into focus. Most importantly, multiple strategies for reducing lipid overload have proven ineffective in preventing the onslaught of neurodegeneration, while efficiently reducing lipid disturbances in extracerebral tissues. Of much significance was the finding that the central nervous system disease is brain autonomous. Finally, investigation of lipid defects and neuropathological changes in Niemann-Pick type C disease gene-1-deficient mice has shed light on some novel putative therapeutic targets.
Summary: The independence of brain pathology from visceral complications in Niemann-Pick type C disease has implications for its treatment. Further studies of the neurological mechanisms underlying the disease will have a significant impact on future clinical diagnosis and management of patients.