Kawano et al., "Phosphorylation by rho kinase regulates CRMP-2 activity in growth cones," Molecular and Cellular Biology, vol.
Kaibuchi, "GSK-3[beta] regulates phosphorylation of CRMP-2 and neuronal polarity," Cell, vol.
PKC appears to also trigger a RhoA-activating cascade through downstream Rho-associated protein kinase (ROCK), which subsequently phosphorylates the collapsin response mediator protein 2 (
CRMP-2) and causes growth cone collapse [127] (Figure 2).
In another study in patients with MTLE associated with hippocampal sclerosis a decreased level of the collapsin response mediated protein-2 (
CRMP-2) was reported [128].
One of the specific substrates that our group has recently defined is CRMP-2 (Figure 3).
It has been hypothesised that GSK-3 overactivity may potentiate sporadic and familial forms of AD by enhancing tau hyperphosphorylation [84] and APP processing and possibly through the phosphorylation of CRMP-2 leading to profound memory impairment [81] (Figures 2 and 3).
According to the company Web site, lacosamide has a novel dual method of action, selectively enhancing slow inactivation of voltage-gated sodium channels, and modulating collapsin response mediator protein 2 (
CRMP-2).
It selectively enhances slow inactivation of sodium channels and interacts with the neuroplasticity-relevant target - collapsin-response mediator protein-2 (
CRMP-2).
Kimura et al., "
CRMP-2 binds to tubulin heterodimers to promote microtubule assembly," Nature Cell Biology, vol.
Li, "GSK-3alpha/beta- mediated phosphorylation of
CRMP-2 regulates activity-dependent dendritic growth," Journal of Neurochemistry, vol.
Wilson et al., "Suppression of inflammatory and neuropathic pain by uncoupling
CRMP-2 from the presynaptic [Ca.sup.2+] channel complex," Nature Medicine, vol.