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Delaying aging and the aging-associated decline in protein homeostasis by inhibition of tryptophan degradation

van der Goot, Annemieke ; Zhu, Wentao ; Vázquez-Manrique, Rafael ; Seinstra, Renée I. ; Dettmer, Katja ; Michels, Helen ; Farina, Francesca ; Krijnen, Jasper ; Melki, Ronald ; Buijsman, Rogier C. ; Ruiz Silva, Mariana ; Thijssen, Karen L. ; Kema, Ido P. ; Neri, Christian ; Oefner, Peter J. ; Nollen, Ellen A. A.


Toxicity of aggregation-prone proteins is thought to play an important role in aging and age-related neurological diseases like Parkinson and Alzheimer's diseases. Here, we identify tryptophan 2,3-dioxygenase (tdo-2), the first enzyme in the kynurenine pathway of tryptophan degradation, as a metabolic regulator of age-related α-synuclein toxicity in a Caenorhabditis elegans model. Depletion of ...


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