From blood to brain: the kynurenine pathway in stress- and age-related diseases

Abstract

Because we are getting older the number of patients with neurodegenerative diseases such as Alzheimer's or Parkinson's is growing. We therefore urgently need ways to diagnose these conditions earlier and to treat them more efficiently. The role of biological ageing in the development of these diseases is an important starting point. Ageing is accompanied by increased metabolism of the amino acid tryptophan. This leads to the accumulation of kynurenines - degradation products of tryptophan. Because certain kynurenines are harmful to the brain, we want to measure the rate of tryptophan metabolism. That's not easy because there are many factors involved. In the first part of this study, we looked at one of these factors: the stress hormone cortisol. It turns out that the more cortisol, the less active tryptophan metabolism. Our research also showed that this relationship can play a role in patient welfare. We know that kynurenines play a role in neurodegenerative diseases. Can they also contribute to the diagnosis or even the treatment? We therefore analysed the concentration of kynurenines in the blood and cerebrospinal fluid of patients with Alzheimer's and Parkinson's disease and in that of healthy elderly. In patients, the concentrations of kynurenic acid - which protects the brain - were very low. We then looked at whether suppressing tryptophan metabolism could have therapeutic value in neurodegenerative diseases. We saw that prolonged suppression partially restores memory capacity in Alzheimer's mice. This may bring us a step closer to unravelling the secrets of neurodegenerative diseases.