Multiple sclerosis (MS) is a multifactorial disease of the central nervous system (CNS) characterized by an inflammatory process and demyelination. The etiology of the disease is still not fully understood. Therefore, finding new etiological factors is of such crucial importance. It is suspected that the development of MS may be affected by oxidative stress (OS). In the acute phase OS initiates inflammatory processes and in the chronic phase it sustains neurodegeneration. Redox processes in MS are associated with mitochondrial dysfunction, dysregulation of axonal bioenergetics, iron accumulation in the brain, impaired oxidant/antioxidant balance, and OS memory. The present paper is a review of the current literature about the role of OS in MS and it focuses on all major aspects. The article explains the mechanisms of OS, reports unique biomarkers with regard to their clinical significance, and presents a poorly understood relationship between OS and neurodegeneration. It also provides novel methods of treatment, including the use of antioxidants and the role of antioxidants in neuroprotection. Furthermore, adding new drugs in the treatment of relapse may be useful. The article considers the significance of OS in the current treatment of MS patients.

The relationship between the prevalence of multiple sclerosis (MS) and sunlight’s ultraviolet radiation was proved. Oxidative stress plays a role in the pathogenic traits of MS. Melatonin possesses antioxidative properties and regulates circadian rhythms. Sleep disturbances in MS patients are common and contribute to daytime fatigue. The aim of study was to evaluate 5 mg daily melatonin supplementation over 90 days on serum total oxidant status (TOS), total antioxidant capacity (TAC) and its influence on sleep quality and depression level of MS patients. A case–control prospective study was performed on 102 MS patients and 20 controls matched for age and sex. The Kurtzke’s Expanded Disability Status Scale, magnetic resonance imaging examinations, Athens Insomnia Scale (AIS), Beck Depression Inventory questionnaires were completed. Serum TOS and TAC levels were measured. We observed higher serum levels of TOS in all MS groups, while after melatonin treatment the TOS levels significantly decreased. The TAC level was significantly lower only in mitoxantrone-treated group and it increased after melatonin supplementation. A strong positive correlation between T1Gd(+) number lesions and TAC level in interferon-beta-1A group was observed. AIS group mean score above 6 defining insomnia were observed in interferon-beta-1B-group, glatiramer acetate-group and mitoxantrone-group: 6.62 ± 2.88, 8.45 ± 2.07, 11.1 ± 3.25, respectively. After melatonin treatment the AIS mean scores decrease in glatiramer acetate-group and mitoxantrone-group achieving 5.25 ± 1.14 and 7.08 ± 2.39, respectively (p < 0.05). Finding from our study suggest that melatonin can act as an antioxidant and improves reduced sleep quality in MS patients.

Aim.Evaluation of the impact of gut microflora on the pathophysiology of MS.Results. The etiopathogenesis of MS is not fully known. Gut microbiota may be of a great importance in the pathogenesis of MS, since recent findings suggest that substitutions of certain microbial population in the gut can lead to proinflammatory state, which can lead to MS in humans. In contrast, other commensal bacteria and their antigenic products may protect against inflammation within the central nervous system. The type of intestinal flora is affected by antibiotics, stress, or diet. The effects on MS through the intestinal microflora can also be achieved by antibiotic therapy andLactobacillus. EAE, as an animal model of MS, indicates a strong influence of the gut microbiota on the immune system and shows that disturbances in gut physiology may contribute to the development of MS.Conclusions.The relationship between the central nervous system, the immune system, and the gut microbiota relates to the influence of microorganisms in the development of MS. A possible interaction between gut microbiota and the immune system can be perceived through regulation by the endocannabinoid system. It may offer an opportunity to understand the interaction comprised in the gut-immune-brain axis.

The Klotho protein is a recently discovered protein and its overexpression is associated with life extension. Klotho deficiency or silencing of the Klotho gene in mice leads to an accelerated aging and short life, whereas overexpression of Klotho in mice extends lifespan. Klotho participates in many metabolic pathways and is highly expressed in the kidneys, the choroid plexus and neurons. It plays a key role in the calcium-phosphate metabolism, remyelination, and cognitive processes. The present paper is a short review of the literature on the role of Klotho in neurodegenerative disorders, with special attention paid to multiple sclerosis. The neuroprotective function of Klotho is also reported. It is also important to consider potential clinical applications of Klotho that might be useful in the treatment of many diseases.

Many studies indicate an important role of microglia and their cytokines in the pathophysiology of multiple sclerosis (MS). Microglia are the macrophages of the central nervous system (CNS). They have many functions, such as being “controllers” of the CNS homeostasis in pathological and healthy conditions, playing a key role in the active immune defense of the CNS. Macroglia exhibit a dual role, depending on the phenotype they adopt. First, they can exhibit neurotoxic effects, which are harmful in the case of MS. However, they also show neuroprotective and regenerative effects in this disease. Many of the effects of microglia are mediated through the cytokines they secrete, which have either positive or negative properties. Neurotoxic and pro-inflammatory effects can be mediated by microglia via lipopolysaccharide and gamma interferon. On the other hand, the mediators of anti-inflammatory and protective effects secreted by microglia can be, for example, interleukin-4 and -13. Further investigation into the role of microglia in MS pathophysiology may perhaps lead to the discovery of new therapies for MS, as recent research in this area has been very promising.