Kinesin Synthesis

Our logic for choosing kinesin for developing CNS therapeutics is based upon our own research, which found that kinesins are transcriptionally upregulated during memory storage and that they are both necessary and sufficient to induce long-term memory storage (LTM) in the marine snail, Aplysia californica (Puthanveettil et al., 2008; Fig 1). Furthermore, other researchers have also discovered that an increase in specific kinesin function in the mouse forebrain improves working memory (Wong et al., 2002; Fig 1). Kinesin is also important in mediating cell division and thus this specific function has been explored for tumor growth inhibition in the development of cancer therapeutics (e.g. Song et al., 2013). These efforts have led to the development of kinesin inhibitors, though none has …show more content…
Our interest is in kinesin activators, which to our knowledge have not been reported, either from academia or from the pharmaceutical industry. Our preliminary results suggest that the activation of specific kinesins is possible, that such activation may have positive effects upon LTM, which is dependent upon effective kinesin function. The goal of this proposal is to assess the ability of the compounds that we have identified from the compound library screen, on enhancing memories in wild type animals and improving memory deficit in AD model mice.

A. PRELIMINARY DATA: The central hypothesis of this proposal is that compounds that activate the motor domain of kinesins will enhance axonal transport and synaptic plasticity; hence such compounds will have memory enhancing properties in intact animals. To identify compounds