In diseases of the central nervous system, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and even epilepsy and migraine, oxidative stress load commonly surpasses endogenous antioxidative capacity. While oxidative processes have been robustly implicated in the pathogenesis of these diseases, the significance of particular antioxidants, both endogenous and especially exogenous, in maintaining redox homeostasis requires further research. Among endogenous antioxidants, enzymes such as catalase, superoxide dismutase, and glutathione peroxidase are central to disabling free radicals, thereby preventing oxidative damage to cellular lipids, proteins, and nucleic acids. Whether supplementation with endogenously occurring antioxidant compounds such as melatonin and glutathione carries any benefit, however, remains equivocal. Similarly, while the health benefits of certain exogenous antioxidants, including ascorbic acid (vitamin C), carotenoids, polyphenols, sulforaphanes, and anthocyanins are commonly touted, their clinical efficacy and effectiveness in particular neurological disease contexts need to be more robustly defined. Here, we review the current literature on the cellular mechanisms mitigating oxidative stress and comment on the possible benefit of the most common exogenous antioxidants in diseases such as AD, PD, ALS, HD, stroke, epilepsy, and migraine. We selected common neurological diseases of a basically neurodegenerative nature.

Rheumatoid arthritis susceptibility genes: An overview

Korczowska I, et al. Yonsei Med J. 2013 Jan;54(1):183-188. https://doi.org/10.3349/ymj.2013.54.1.183

Autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited vascular disease characterized by recurrent strokes, cognitive impairment, psychiatric symptoms, apathy, and migraine. Approximately 40% of patients with CADASIL experience migraine with aura (MA). In addition to MA, CADASIL patients are described in the literature as having migraine without aura (MO) and other types of headaches. Mutations in the NOTCH3 gene cause CADASIL. This study investigated NOTCH3 genetic variants in CADASIL patients and their potential association with headache types. Genetic tests were performed on 30 patients with CADASIL (20 women aged 43.6 ± 11.5 and 10 men aged 39.6 ± 15.8). PCR-HRM and sequencing methods were used in the genetic study. We described three variants as pathogenic/likely pathogenic (p.Tyr189Cys, p.Arg153Cys, p.Cys144Arg) and two benign variants (p.Ala202=, p.Thr101=) in the NOTCH3 gene and also presented the NOTCH3 gene variant (chr19:15192257 T>G). Clinical features including headache associated with NOTCH3 (chr19:15192257 T>G) are described for the first time. Patients with pathogenic/likely pathogenic variants had similar headache courses. People with benign variants showed a more diverse clinical picture. It seems that different NOTCH3 variants may contribute to the differential presentation of a CADASIL headache, highlighting the diagnostic and prognostic value of headache characteristics in this disease.