Recent Advances on Immunosuppressive Drugs and Remyelination Enhancers for the Treatment of Multiple Sclerosis

Mammalian nervous systems depend crucially on myelin sheaths covering the axons. In the central nervous system, myelin sheaths consist of lipid structures that are generated from the membrane of oligodendro-cytes (OL). These sheaths allow fast nerve transmission, protect axons and provide them metabolic support. In response to specific traumas or pathologies, these lipid structures can be destabilized and generate demyelinat-ing lesions. Multiple sclerosis (MS) is an example of a demyelinating disease in which the myelin sheaths sur-rounding the nerve fibers of the brain and spinal cord are damaged. MS is the leading cause of neurological disability in young adults in many countries, and its incidence has been increasing in recent decades. Related to its etiology, it is known that MS is an autoimmune and inflammatory CNS disease. However, there are no effective treatments for this disease and the immunomodulatory therapies that currently exist have proven limited success since they only delay the progress of the disease. Nowadays, one of the main goals in MS research is to find treatments which allow the recovery of neurological disabilities due to demyelination. To this end, different approaches, such as modulating intracellular signaling or regulating the lipid metabolism of OLs, are being considered. Here, in addition to immunosuppressive or immunomodulatory drugs that reduce the immune response against myelin sheaths, we review a diverse group of drugs that promotes endogenous remyelination in MS patients and their use may be interesting as potential therapeutic agents in MS disease. To this end, we compile specific treatments against MS that are currently in the market with remyelination strategies that have entered into human clinical trials for future reparative MS therapies. The method used in this study is a systematic literature review on PubMed, Web of Science and Science Direct databases up to May 31, 2020. To narrow down the search results in databases, more specific keywords, such as “myelin sheath”, “remyelination”, “de-myelination”, “oligodendrocyte” and “lipid synthesis” were used to focus the search. We preferred papers pub-lished after January 2015, but did not exclude earlier seminal papers

Fatty Acids and Antioxidants in Multiple Sclerosis: Therapeutic Role of GEMSP

[EN] Multiple sclerosis is a high-frequency neurological disorder in young adults. Although there are some genetic and environmental factors that have been related to the onset of the disease, these are still not completely understood and nowadays multiple sclerosis can neither be prevented, nor its symptom effectively treated due to disease heterogeneity. For this reason, the search of prognostic factors and new therapeutic compounds for MS has long aroused among clinicians and researchers. Among these therapeutic compounds, GEMSP, which consists of a mixture of functional constituents as fatty acids, antioxidants, free radical scavengers and amino acids linked individually to poly-L-Lysine (PL), is emerging as a promising drug for MS treatment. Pre-clinical studies using GEMSP have demonstrated that this drug strongly inhibits brain leukocyte infiltration and completely abolishes experimental autoimmune encephalomyelitis. In addition, in an open clinical trial in humans treated with GEMSP, in 72% of the cases, a positive evolution of the state of the MS patients treated with GMSP was observed. In this review a biochemical characterization of main constituents of GEMSP, which include fatty acids as oleic acid, linoleic acid or azelaic acid and the antioxidants alpha-tocopherol or ascorbic acid, will be provided in order to understand their proved therapeutic effects in MS

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field