New AD drug

Michelle Anne Freeman maf2d at galen.med.Virginia.EDU
Fri Sep 23 22:06:11 EST 1994

Several people expressed interest in having this reference, so
I'm posting it for general consumption:

H. Geerts, R. Nuydens, R. Nuyens, F. Cornelissen, M. De
Brabander, P. Pauwels, P.A.J. Janssen, Y.H. Song, and E.M.
Mandelkow.  Sabeluzole, a memory-enhancing molecule, increases
fast axonal transport in neuronal cell cultures.  _Experimental
Neurology_ 117: 36-43 (1992).

Abstract:  Morphological rearrangements, such as synapse number
changes, have been observed in the adult mammalian brain after
various experimental paradigms of learning and behavioral
experience.  The role of axonal transport in the physical
translocation of material during this form of brain plasticity
has not been fully appreciated.  We show here by quantitative
video microscopy that sabeluzole (R58735), a new
memeory-enhancing drug in humans, effectively increases fast
axonal transport in rat neuronal cell cultures.  Long-term
incubation (24 hr) with sabeluzole in the concentration range
between 0.1 and 1 uM increases both velocity and jump length of
saltatory movements maximally by 20-30% in embryonic
hippocampal neurons.  Acute treatment only increases the
velocity by 15-20%.  Furthermore, the inhibition of axonal
transport by 0.1mM vanadate in N4 neuroblastoma cells is
reversed by 1uM sabeluzole.  Observations on the
kinesin-induced microtubule mobility in a reconstituted system
show a 10% enhancement by sabeluzole at an optimal
concentration of 2uM, but no increase in kinesin ATPase
activity.  To our knowledge, this is the first pharmacological
compound shown to increase fast axonal transport.  The
mechanism of fast axonal transport enhancement is discussed as
a rationale for new therapeutic treatment in neuropathology.

Michelle Freeman				 o o
MSTP/Neurosciences Graduate Student 		\   /------
maf2d at galen.med.virginia.edu			|\_/|-\--
						|   |  \    

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