The role of blood brain barrier (BBB) is to preserve a precisely regulated environment for proper neuronal signaling. In many of the central nervous system (CNS) pathologies, the function of BBB is altered. Thus, there is a necessity to evaluate a fast, noninvasive and reliable method for monitoring of BBB condition. It seems that revealing the peripheral diagnostic biomarker whose release pattern (concentration, dynamics) will be correlated with clinical symptoms of neurological disorders offers significant hope. It could help with faster diagnosis and efficient treatment monitoring. In this review we summarize the recent data concerning exploration of potential new serum biomarkers appearing in the peripheral circulation following BBB disintegration, with an emphasis on epilepsy, traumatic brain injury (TBI) and stroke. We consider the application of well-known proteins (S100β and GFAP) as serum indicators in the light of recently obtained results. Furthermore, the utility of molecules like MMP-9, UCHL-1, neurofilaments, BDNF, and miRNA, which are newly recognized as a potential serum biomarkers, will also be discussed.
: Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by a mutation in the gene that encodes a critical cell regulatory protein, huntingtin (Htt). The expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats causes improper folding of functional proteins and is an initial trigger of pathological changes in the brain. Recent research has indicated that the functional dysregulation of many transcription factors underlies the neurodegenerative processes that accompany HD. These disturbances are caused not only by the loss of wild-type Htt (WT Htt) function but also by the occurrence of abnormalities that result from the action of mutant Htt (mHtt). : In this review, we aim to describe the role of transcription factors that are currently thought to be strongly associated with HD pathogenesis, namely, RE1-silencing transcription factor, also known as neuron-restrictive silencer factor (REST/NRSF), forkhead box proteins (FOXPs), peroxisome proliferator-activated receptor gamma coactivator-1a (PGC1α), heat shock transcription factor 1 (HSF1), and nuclear factor κ light-chain-enhancer of activated B cells (NF- κB). We also take into account the role of these factors in the phenotype of HD as well as potential pharmacological interventions targeting the analyzed proteins. Furthermore, we considered whether molecular manipulation resulting in changes in transcription factor function may have clinical potency for treating HD.
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) that mostly manifests as irreversible disability. The aetiopathogenesis of MS is still unclear, although it was initially thought to be primarily mediated by T-cells. Research into the immune concepts of MS pathophysiology in recent years has led to a shift in the understanding of its origin i.e. from a T-cell-mediated to a B-cell-mediated molecular background. Thus, the use of B-cell-selective therapies, such as anti- -CD20 antibody therapy, as expanded therapeutic options for MS is now strongly supported. This review provides an up-to-date discussion on the use of anti-CD20 targeted therapy in MS treatment. We present a rationale for its use and summarise the results of the main clinical trials showing the efficacy and safety of rituximab, ocrelizumab, ofatumumab, and ublituximab. Future directions that show selectivity to a broader population of lymphocytes, such as the use of anti-CD19 targeted antibodies, as well as the concept of extended interval dosing (EID) of anti-CD20 drugs, are also discussed in this review Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) that mostly manifests as irreversible disability. The aetiopathogenesis of MS is still unclear, although it was initially thought to be primarily mediated by T-cells. Research into the immune concepts of MS pathophysiology in recent years has led to a shift in the understanding of its origin i.e. from a T-cell-mediated to a B-cell-mediated molecular background. Thus, the use of B-cell-selective therapies, such as anti- -CD20 antibody therapy, as expanded therapeutic options for MS is now strongly supported. This review provides an up-to-date discussion on the use of anti-CD20 targeted therapy in MS treatment. We present a rationale for its use and summarise the results of the main clinical trials showing the efficacy and safety of rituximab, ocrelizumab, ofatumumab, and ublituximab. Future directions that show selectivity to a broader population of lymphocytes, such as the use of anti-CD19 targeted antibodies, as well as the concept of extended interval dosing (EID) of anti-CD20 drugs, are also discussed in this review