As human life expectancy has improved rapidly in industrialized societies, age-related\ncognitive impairment presents an increasing challenge. Targeting histopathological processes\nthat correlate with age-related cognitive declines, such as neuroinflammation, low levels of\nneurogenesis, disrupted bloodââ?¬â??brain barrier and altered neuronal activity, might lead to\nstructural and functional rejuvenation of the aged brain. Here we show that a 6-week\ntreatment of young (4 months) and old (20 months) rats with montelukast, a marketed\nanti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates\nhippocampal neurogenesis and improves learning and memory in old animals. By using gene\nknockdown and knockout approaches, we demonstrate that the effect is mediated through\ninhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor\nsignalling might represent a safe and druggable target to restore cognitive functions in old\nindividuals and paves the way for future clinical translation of leukotriene receptor inhibition\nfor the treatment of dementias.
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