Modelling the neurodevelopmental pathogenesis in neuropsychiatric disorders. Bioactive kynurenines and their analogues as neuroprotective agents-in celebration of 80th birthday of Professor Peter Riederer.

Abstract

Following introduction of the monoamine oxidase type B inhibitor selegiline for the treatment of Parkinson's disease (PD), discovery of the action mechanism of Alzheimer's disease-modifying agent memantine, the role of iron in PD, and the loss of electron transport chain complex I in PD, and development of the concept of clinical neuroprotection, Peter Riederer launched one of the most challenging research project neurodevelopmental aspects of neuropsychiatric disorders. The neurodevelopmental theory holds thata disruption of normal brain development in utero or during early life underlies the subsequent emergence of neuropsychiatric symptoms during later life. Indeed, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Classification of Diseases, 11thRevision categorize autism spectrum disorder and attention deficit hyperactivity disorder in neurodevelopmental disorders (NDDs). More and more evidence, especially from preclinical studies, is revealing that neurodevelopmental pathology is not limited to the diagnostic class above, but also contributes to the development of other psychiatric disorders such as schizophrenia, bipolar disorder, and obsessive-compulsivedisorder as well as neurodegenerative diseases such as PD and Huntington's disease. Preclinical animal research is taking a lead in understanding the pathomechanisms of NDDs, searching for novel targets, and developing new neuroprotective agents against NDDs. This narrative review discusses emerging evidence of the neurodevelopmental etiology of neuropsychiatric disorders, recent advances in modelling neurodevelopmental pathogenesis, potential strategies of clinical neuroprotection using novel kynurenine metabolites and analogues, and future research direction for NDDs.