The potential role of kynurenines in Alzheimer’s disease: pathomechanism and therapeutic possibilities by influencing the glutamate receptors

Abstract

The pathomechanism of neurodegenerative disorders still poses a challenge to neuroscientists, and continuous research is under way with the aim of attaining an understanding of the exact background of these devastating diseases. The pathomechanism of Alzheimer's disease (AD) is associated with characteristic neuropathological features such as extracellular amyloid-β and intracellular tau deposition. Glutamate excitotoxicity and neuroinflammation are also factors that are known to contribute to the neurodegenerative process, but a cerebrovascular dysfunction has recently also been implicated in AD. Current therapeutic tools offer moderate symptomatic treatment, but fail to reduce disease progression. The kynurenine pathway (KP) has been implicated in the development of neurodegenerative processes, and alterations in the KP have been demonstrated in both acute and chronic neurological disorders. Kynurenines have been suggested to be involved in the regulation of neurotransmission and in immunological processes. Targeting the KP, therefore, offers a valuable strategic option for the attenuation of glutamatergic excitotoxicity, and for neuroprotection.