Recent studies of the low abundant signaling lipid, phosphatidylinositol 3,5‐bisphosphate (PI(3,5)P2), reveal an intriguingly diverse list of downstream pathways, the intertwined relationship between PI(3,5)P2 and PI5P, as well as links to neurodegenerative diseases. Derived from the structural lipid phosphatidylinositol, PI(3,5)P2 is dynamically generated on multiple cellular compartments where interactions with an increasing list of effectors regulate many cellular pathways. A complex of proteins that includes Fab1/PIKfyve, Vac14, and Fig4/Sac3 mediates the biosynthesis of PI(3,5)P2, and mutations that disrupt complex function and/or (...) formation cause profound consequences in cells. Surprisingly, mutations in this pathway are linked with neurological diseases, including Charcot‐Marie‐Tooth syndrome and amyotrophic lateral sclerosis. Future studies of PI(3,5)P2 and PI5P are likely to expand the roles of these lipids in regulation of cellular functions, as well as provide new approaches for treatment of some neurological diseases. (shrink)

Neurofilaments are one of the major components of the neuronal cytoskeleton and are responsible for maintaining the calibre of axons. They are modified by post‐translational changes that are regulated in complex fashions including by the interaction with neighbouring glial cells. Neurofilament accumulations are seen in several neurological diseases and neurofilament mutations have now been associated with Charcot‐Marie‐Tooth disease, Parkinson's disease and amyotrophic lateral sclerosis. In this review, we discuss the structure, normal function and molecular pathology of neurofilaments. BioEssays 25:346–355, (...) 2003. © 2003 Wiley Periodicals, Inc. (shrink)