Tryptophan Metabolism Through the Kynurenine Pathway in Glial Cells

Neuroglia, Journal Year: 2025, Volume and Issue: 6(1), P. 14 - 14

Published: March 12, 2025

The central nervous system (CNS) relies on complex and dynamic interactions between neurons glial cells. Among cells, astrocytes regulate the chemical environment surrounding supply essential nutrients for brain metabolism whereas microglia, resident macrophages of CNS, play critical roles in homeostasis, defense, responses to injury. Both microglia contribute regulation excitotoxicity inflammation mediated by tryptophan (Trp) via kynurenine pathway. Trp generates several bioactive metabolites, including quinolinic acid (QUIN) kynurenic (KYNA), which have opposing effects. QUIN, produced activated acts as an agonist NMDA receptors; excessive stimulation these receptors can lead neuronal death. Conversely, KYNA, primarily 2,3-aminotransferases (KAT), receptor antagonist, conferring neuroprotection mitigating excitotoxicity. Dysregulation is implicated many neurodegenerative diseases such Alzheimer’s disease, Parkinson’s multiple sclerosis amyotrophic lateral sclerosis, well various neuropsychiatric disorders. This review examines cellular molecular mechanisms underlying highlighting unique contributions each phenotype, implications CNS pathologies, potential biomarkers therapeutic targets restoring homeostasis preventing disease progression.

Language: Английский

Nilotinib as a Prospective Treatment for Alzheimer’s Disease: Effect on Proteins Involved in Neurodegeneration and Neuronal Homeostasis

Life, Journal Year: 2024, Volume and Issue: 14(10), P. 1241 - 1241

Published: Sept. 28, 2024

Nilotinib, a tyrosine kinase inhibitor that targets the Abelson (c-Abl) signaling pathway, is FDA-approved to treat chronic myeloid leukemia. Nilotinib has properties indicative of possible utility in neuroprotection have prompted exploration repurposing drug for treatment Alzheimer's disease (AD) and Parkinson's (PD). AD progressive age-related neurodegenerative disorder characterized by deposition extracellular amyloid-β plaques intracellular neurofibrillary tangles. It incurable affects approximately 50 million patients worldwide. reduces c-Abl phosphorylation, levels, dopaminergic neuron degeneration preclinical models. This study explores effects nilotinib on amyloid processing mitochondrial functioning SH-SY5Y human neuroblastoma cell line. cells were exposed (1, 5, 10 µM). Real-time PCR immunoblot analysis performed quantify expression genes pertaining neuronal health. did not significantly change APP, BACE1, or ADAM10 mRNA levels. However, BACE1 protein was increased at 1 µM, µM without affecting APP expression. Further, affect associated with health functioning. Taken together, our findings do support efficacy neuroprotection.

Language: Английский

NSE and S100β as serum alarmins in predicting neurological outcomes after cardiac arrest

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 26, 2024

Language: Английский