Crosstalk Between the Immune and Central Nervous Systems with Special Reference to Drug Development

Although the understanding of disease mechanisms becomes rapidly progressed in recent years, there remain a lot of unmet medical needs in a number of disease fields. Especially in the degenerative diseases of the central nervous system (CNS) such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, stroke and traumatic brain injury, currently available drugs only manage the symptoms, and there exist few disease-modifying therapies. Therefore, novel therapeutic interventions that modify and delay the disease progression are highly demanded. Drug development for the CNS diseases is particularly challenging (Kola I and Landis J, 2004). One of the hurdles to develop drugs for the CNS diseases is poor translation from animal models to human diseases (Pritchard JF, 2008). One strategy to overcome this hurdle is to examine therapeutic potential of a target molecule in a number of experimental settings, assuming that a molecule that modulates pathophysiologic mechanisms underlying a range of neurodegenerative disease has a higher chance to work in human disease (Mehal WZ, Iredale J & Friedman SL 2011). Although this strategy requires much resource, it enables us to eliminate candidates that act only in a particular experimental setting that might have a lower chance to be effective in humans. One example for this strategy is a kynurenine 3-monooxygenase that catalyzes the conversion of kynurenine to 3-hydroxykynurenine in the kynurenine pathway of tryptophan degradation (Stone TW & Darlington LG, 2002; Schwarcz R, 2004). A small molecule inhibitor of kynurenine 3-monooxygenase increased the levels of neuroprotective kynurenic acid and decreased the levels of neurotoxic quinolinic acid/3-hydroxykynurenine in mice. Furthermore, the treatment with the kynurenine 3-monooxygenase inhibitor ameliorated neurodegeneration in two types of mouse neurodegenerative models for Alzheimer’s disease and Huntington’s disease (Reinhart PH & Kelly JW, 2011; Zwilling D et al., 2011). These observations suggest that the kynurenine 3-monooxygenase would be more promising therapeutic target than conventional therapeutic ones that are effective in animal models of a single disease. Another strategy to increase the probability of success of drug development in the CNS diseases is to target a molecule that possess multiple pharmacological actions and hence