The kynurenine pathway (KP) is the main route of tryptophan degradation whose final product is NAD+. The metabolism of tryptophan can be altered in ageing and with neurodegenerative process, leading to decreased biosynthesis of nicotinamide. This fact is very relevant considering that tryptophan is the major source of body stores of the nicotinamide-containing NAD+ coenzymes, which is involved in almost all the bioenergetic and biosynthetic metabolism. Recently, it has been proposed that endogenous tryptophan and its metabolites can interact and/or produce reactive oxygen species in tissues and cells. This subject is of great importance due to the fact that oxidative stress, alterations in KP metabolites, energetic deficit, cell death, and inflammatory events may converge each other to enter into a feedback cycle where each one depends on the other to exert synergistic actions among them. It is worth mentioning that all these factors have been described in aging and in neurodegenerative processes; however, has so far no one established any direct link between alterations in KP and these factors. In this review, we describe each kynurenine remarking their redox properties, their effects in experimental models, their alterations in the aging process.

Huntington’s disease (HD) is an inheritable autosomal-dominant disorder whose causal mechanisms remain unknown. Experimental models have begun to uncover these pathways, thus helping to understand the mechanisms implicated and allowing for the characterization of potential targets for new therapeutic strategies. 3-Nitropropionic acid is known to produce in animals behavioural, biochemical and morphologic changes similar to those occurring in HD. For this reason, this phenotypic model is gaining attention as a valuable tool to mimick this disorder and further developing new therapies. In this review, we will focus on the past and present research of this molecule, to finally bring a perspective on what will be next in this promising field of study.

Glioblastoma multiforme (GBM) is a highly aggressive neoplasia, prognosis remains dismal, and current therapy is mostly palliative. There are no known risk factors associated with gliomagenesis; however, it is well established that chronic inflammation in brain tissue induces oxidative stress in astrocytes and microglia. High quantities of reactive species of oxygen into the cells can react with several macromolecules, including chromosomal and mitochondrial DNA, leading to damage and malfunction of DNA repair enzymes. These changes bring genetic instability and abnormal metabolic processes, favoring oxidative environment and increase rate of cell proliferation. In GBM, a high metabolic rate and increased basal levels of reactive oxygen species play an important role as chemical mediators in the regulation of signal transduction, protecting malignant cells from apoptosis, thus creating an immunosuppressive environment. New redox therapeutics could reduce oxidative stress preventing cellular damage and high mutation rate accompanied by chromosomal instability, reducing the immunosuppressive environment. In addition, therapies directed to modulate redox rate reduce resistance and moderate the high rate of cell proliferation, favoring apoptosis of tumoral cells. This review describes the redox status in GBM, and how this imbalance could promote gliomagenesis through genomic and mitochondrial DNA damage, inducing the pro-oxidant and proinflammatory environment involved in tumor cell proliferation, resistance, and immune escape. In addition, some therapeutic agents that modulate redox status and might be advantageous in therapy against GBM are described.

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