Status message

We are currently rebuilding the search index. Some search results may be inaccurate or incomplete.

. A role for motoneuron subtype-selective ER stress in disease manifestations of FALS mice. Nat Neurosci. 2009 May;12(5):627-36. PubMed.


Please login to recommend the paper.


Make a Comment

To make a comment you must login or register.

Comments on this content

  1. While appreciating the impressive FALS study by Sexena et al., I could not help frowning on the comment by P.F. Jennings: Why implicate protein tau and axonal transport? Tau-4R transgenic mice develop axonopathy leading to Wallerian degeneration and muscle wasting, but not premature death (Spittaels et al., 1999), as opposed to tau-P301L mice that develop tauopathy and die prematurely (Terwel et al., 2005).

    Both patho-phenotypes are affected by co-expression of GSK3, albeit quite differently: rescue and aggravation of tauopathy, respectively (Spittaels et al., 2000; Terwel et al., 2008).

    Our simplest explanation: excess tau-4R (but not tau-P301L) occupies microtubular binding sites, preventing motor proteins to walk and transport "stuff." GSK3 phosphorylates tau and releases it from the MT to allow transport again, but thereby causes tauopathy at the expense of axonopathy. Why motor neurons are most sensitive to tau-induced degeneration remains an open question. Caroni and co-workers provide possible indications.

    But is protein tau involved in ALS?


    . Prominent axonopathy in the brain and spinal cord of transgenic mice overexpressing four-repeat human tau protein. Am J Pathol. 1999 Dec;155(6):2153-65. PubMed.

    . Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice. J Biol Chem. 2000 Dec 29;275(52):41340-9. PubMed.

    . Changed conformation of mutant Tau-P301L underlies the moribund tauopathy, absent in progressive, nonlethal axonopathy of Tau-4R/2N transgenic mice. J Biol Chem. 2005 Feb 4;280(5):3963-73. PubMed.

    . Amyloid activates GSK-3beta to aggravate neuronal tauopathy in bigenic mice. Am J Pathol. 2008 Mar;172(3):786-98. PubMed.