The complexity of a monogenic neurodegenerative disease: More than two decades of therapeutic driven research into Niemann-Pick type C disease.

Authors:
Natalie Hammond
Natalie Hammond
Victoria University of Wellington
Wellington | New Zealand
Andrew B Munkacsi
Andrew B Munkacsi
Columbia University Medical Center
United States
Stephen L Sturley
Stephen L Sturley
Columbia University Medical Center
United States

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 17;1864(8):1109-1123. Epub 2019 Apr 17.

Department of Biology, Barnard College-Columbia University, New York, NY 10027, United States of America. Electronic address:

Niemann-Pick type C (NP-C) disease is a rare and fatal neurodegenerative disease typified by aberrations in intracellular lipid transport. Cholesterol and other lipids accumulate in the late endosome/lysosome of all diseased cells thereby causing neuronal and visceral atrophy. A cure for NP-C remains elusive despite the extensive molecular advances emanating from the identification of the primary genetic defect in 1997. Penetration of the blood-brain barrier and efficacy in the viscera are prerequisites for effective therapy, however the rarity of NP-C disease is the major impediment to progress. Disease diagnosis is challenging and establishment of appropriate test populations for clinical trials difficult. Fortunately, disease models that span the diversity of microbial and metazoan life have been utilized to advance the quest for a therapy. The complexity of lipid storage in this disorder and in the model systems, has led to multiple theories on the primary disease mechanism and consequently numerous and varied proposed interventions. Here, we conduct an evaluation of these studies.

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Source
http://dx.doi.org/10.1016/j.bbalip.2019.04.002DOI Listing
April 2019
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