Tryptophan metabolism in the central nervous system: medical implications

The metabolism of the amino acid L-tryptophan is a highly regulated physiological process leading to the generation of several neuroactive compounds within the central nervous system. These include the aminergic neurotransmitter serotonin (5-hydroxytryptamine, 5-HT), products of the kynurenine pathway of tryptophan metabolism (including 3-hydroxykynurenine, 3-hydroxyanthranilic acid, quinolinic acid and kynurenic acid), the neurohormone melatonin, several neuroactive kynuramine metabolites of melatonin, and the trace amine tryptamine. The integral role of central serotonergic systems in the modulation of physiology and behaviour has been well documented since the first description of serotonergic neurons in the brain some 40 years ago. However, while the significance of the peripheral kynurenine pathway of tryptophan metabolism has also been recognised for several decades, it has only recently been appreciated that the synthesis of kynurenines within the central nervous system has important consequences for physiology and behaviour. Altered kynurenine metabolism has been implicated in the pathophysiology of conditions such as acquired immunodeficiency syndrome (AIDS)-related dementia, Huntington's disease and Alzheimer's disease. In this review we discuss the molecular mechanisms involved in regulating the metabolism of tryptophan and consider the medical implications associated with dysregulation of both serotonergic and kynurenine pathways of tryptophan metabolism

Complexity not collapse: recasting the geographies of homelessness in a ‘punitive’ age

Over the past decade there has been a proliferation of work on homelessness by geographers.Much of this has been framed by the desire to connect discussions of homelessness to wider debates around gentrifi cation, urban restructuring and the politics of public space. Though such work has been helpful in shifting discussions of homelessness into the mainstream geographical literature, too much of it remains narrowly framed within a US metric of knowledge and too closely focused upon the recent punitive turn in urban social policy. Here we advance instead a framework that recognizes the growing multiplicy of homeless geographies in recent years under policies that are better understood as multifaceted and ambivalent rather than only punitive