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Trends Neurosci. 2014 Feb;37(2):66-76. doi: 10.1016/j.tins.2013.11.006. Epub 2014 Jan 8.

Stuck in traffic: an emerging theme in diseases of the nervous system.

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Division of Cell Biology, Netherlands Cancer Institute, 1066CX Amsterdam, The Netherlands. Electronic address:
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA. Electronic address:


The past decade has seen an explosion of DNA sequencing activities and many mutations and genetic variances underlying neurological and neurodegenerative diseases have been determined. This wealth of genetic data is now placed in molecular pathways revealing the nodes that underlie the disrupted processes. Many mutations in neurological diseases affect proteins controlling endosomal/lysosomal transport. Although the age of onset of these diseases range from juvenile [i.e., Niemann-Pick type C (NPC) and Charcot-Marie-Tooth (CMT) disease] to late onset (Parkinson's and Alzheimer's disease), deregulation of endosomal transport is a common theme. This review summarizes how elucidating the genetic basis for the various neurological diseases has advanced our understanding of the endo-lysosomal system and why the various mutations all translate into similar disease phenotypes.


Alzheimer's disease; Charcot-Marie-Tooth disease; Parkinson's disease; amyothoropic lateral sclerosis; endo-lysosomal system; hereditary spastic paraplegia; neurological disease; protein trafficking

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