Tryptophan metabolites modify brain Aβ peptide degradation: A role in Alzheimer’s disease?

摘要: Abstract Among several processes, a decrease in amyloid-beta (Aβ) peptide elimination is thought to be one of the major pathophysiological factors Alzheimer’s disease (AD). Neprilysin (NEP) key metalloproteinase controlling degradation and clearance Aβ peptides brain. NEP induced by pharmacological substances, amyloid deposits somatostatin, but physiological regulation its expression remains unclear. This situation hampers exploitation regulatory factors/mechanisms develop effective strategies against accumulation-induced brain toxicity. Based on recent data aimed at elucidating this question, present paper addresses critically discusses role 5-hydroxyindole-acetic acid (5-HIAA) kynurenic (KYNA) activity/expression Both 5-HIAA KYNA are endogenous metabolites tryptophan, an essential amino-acid obtained through diet gut microbiome. By interacting with aryl hydrocarbon receptor, various tryptophan modulate metalloproteinases regulating levels under normal pathological conditions such as AD. In particular, interesting reviewed here show that stimulate prevent peptide-induced neurotoxicity. These open promising perspectives for development metabolite-based therapies