Rollercoaster ride of kynurenines: steering the wheel towards neuroprotection in Alzheimer's disease

Introduction: Alzheimer's disease (AD) is associated with cerebral cognitive deficits exhibiting two cardinal hallmarks: accruement of extracellular amyloid plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. The currently accessible therapeutic armamentarium merely provides symptomatic relief. Therefore, the cry for prospective neuroprotective strategies seems to be the need of the hour. Areas covered: This review comprehensively establishes correlation between kynurenine pathway (KP) metabolites and AD with major emphasis on its two functionally contrasting neuroactive metabolites i.e. kynurenic acid (KYNA) and quinolinic acid (QUIN) and enlists various clinical studies which hold a potential for future therapeutics in AD. Also, major hypotheses of AD and mechanisms underlying them have been scrutinized with the aim to brush up the readers with basic pathology of AD. Expert opinion: KP is unique in itself as it holds two completely different domains i.e. neurotoxic QUIN and neuroprotective KYNA and disrupted equilibrium between the two has a hand in neurodegeneration. KYNA has long been demonstrated to be neuroprotective but lately being disparaged for cognitive side effects. But we blaze a trail by amalgamating the pharmacological mechanistic studies of KYNA in kinship with alpha 7nAChRs, NMDARs and GABA which lends aid in favour of KA.