Microbiota, Tryptophan and Aryl Hydrocarbon Receptors as the Target Triad in Parkinson’s Disease—A Narrative Review

In the era of a steadily increasing lifespan, neurodegenerative diseases among the elderly present a significant therapeutic and socio-economic challenge. A properly balanced diet and microbiome diversity have been receiving increasing attention as targets for therapeutic interventions in neurodegeneration. Microbiota may affect cognitive function, neuronal survival and death, and gut dysbiosis was identified in Parkinson’s disease (PD). Tryptophan (Trp), an essential amino acid, is degraded by microbiota and hosts numerous compounds with immune- and neuromodulating properties. This broad narrative review presents data supporting the concept that microbiota, the Trp-kynurenine (KYN) pathway and aryl hydrocarbon receptors (AhRs) form a triad involved in PD. A disturbed gut–brain axis allows the bidirectional spread of pro-inflammatory molecules and α-synuclein, which may contribute to the development/progression of the disease. We suggest that the peripheral levels of kynurenines and AhR ligands are strongly linked to the Trp metabolism in the gut and should be studied together with the composition of the microbiota. Such an approach can clearly delineate the sub-populations of PD patients manifesting with a disturbed microbiota–Trp-KYN–brain triad, who would benefit from modifications in the Trp metabolism. Analyses of the microbiome, Trp-KYN pathway metabolites and AhR signaling may shed light on the mechanisms of intestinal distress and identify new targets for the diagnosis and treatment in early-stage PD. Therapeutic interventions based on the combination of a well-defined food regimen, Trp and probiotics seem of potential benefit and require further experimental and clinical research

The Role of Cocaine- and Amphetamine-Regulated Transcript (CART) in Cancer: A Systematic Review

The functions of cocaine- and amphetamine-regulated transcript (CART) neuropeptide encoded by the CARTPT gene vary from modifying behavior and pain sensitivity to being an antioxidant. Putative CART peptide receptor GPR160 was implicated recently in the pathogenesis of cancer. However, the exact role of CART protein in the development of neoplasms remains unclear. This systematic review includes articles retrieved from the Scopus, PubMed, Web of Science and Medline Complete databases. Nineteen publications that met the inclusion criteria and describe the association of CART and cancer were analyzed. CART is expressed in various types of cancer, e.g., in breast cancer and neuroendocrine tumors (NETs). The role of CART as a potential biomarker in breast cancer, stomach adenocarcinoma, glioma and some types of NETs was suggested. In various cancer cell lines, CARTPT acts an oncogene, enhancing cellular survival by the activation of the ERK pathway, the stimulation of other pro-survival molecules, the inhibition of apoptosis or the increase in cyclin D1 levels. In breast cancer, CART was reported to protect tumor cells from tamoxifen-mediated death. Taken together, these data support the role of CART activity in the pathogenesis of cancer, thus opening new diagnostic and therapeutic approaches in neoplastic disorders