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Conductive biomaterials provide an important control for engineering neural tissues, where electrical stimulation can potentially direct neural stem/progenitor cell (NS/PC) maturation into functional neuronal networks. It is anticipated that stem cell-based therapies to repair damaged central nervous system (CNS) tissues and ex vivo, "tissue chip" models of the CNS and its pathologies will each benefit from the development of biocompatible, biodegradable, and conductive biomaterials. Here, technological advances in conductive biomaterials are reviewed over the past two decades that may facilitate the development of engineered tissues with integrated physiological and electrical functionalities. First, one briefly introduces NS/PCs of the CNS. Then, the significance of incorporating microenvironmental cues, to which NS/PCs are naturally programmed to respond, into biomaterial scaffolds is discussed with a focus on electrical cues. Next, practical design considerations for conductive biomaterials are discussed followed by a review of studies evaluating how conductive biomaterials can be engineered to control NS/PC behavior by mimicking specific functionalities in the CNS microenvironment. Finally, steps researchers can take to move NS/PC-interfacing, conductive materials closer to clinical translation are discussed.

• Sirtuins have critical roles in the central nervous system, immune system and metabolism. • Based on animal experiments SIRTs seems as novel candidates of therapeutic targets in MS. • Here some rational for selecting sirtuins as therapeutic targets in MS disease are presented. • The lack of clinical evidence for the role of some sirtuins in MS is highlighted. Multiple Sclerosis (MS) is a challenging and disabling condition particularly in the secondary progressive (SP) phase of this disease. The available treatments cannot ameliorate or stop disease progression in this phase, and there is an urgent need to focus on effective therapies and the molecular pathways involved SPMS. Given the significant impact of neurodegeneration, autoimmunity and metabolic alterations in MS, focusing on the molecules that target these different pathways could help in finding new treatments. Sirtuins (SIRTs) are NAD+ dependent epigenetic and metabolic regulators, which have critical roles in the physiology of central nervous system, immune system and metabolism. Based on these facts, SIRTs are crucial candidates of therapeutic targets in MS and collecting the information related to MS disease for each SIRT individually is noteworthy and highlights the lack of investigation in each part. In this review we summarized the role of different sirtuins as key regulator in neurodegeneration, autoimmunity and metabolism pathways. We also clarify the rationale behind selecting SIRTs as therapeutic targets in MS disease by collecting the researches showing alteration of these proteins in human samples of MS patients and animal model of MS, and also the improvement of modeled animals after SIRT-directed treatments. [ABSTRACT FROM AUTHOR]

Glutamate in excessive amounts is a major contributor to neuronal degeneration, and its removal is attributed mainly to astrocytes. Traumatic injury to the central nervous system (CNS) is often accompanied by disappearance of astrocytes from the lesion site and failure of the remaining cells to withstand the ensuing toxicity. Microglia that repopulate the lesion site are the usual suspects for causing redox imbalance and inflammation and thus further exacerbating the neurotoxicity. However, our group recently demonstrated that early post-injury activation of microglia as antigen-presenting cells correlates with an ability to withstand injurious conditions. Moreover, we found that T cells reactive to CNS-specific self-antigens protected neurons against glutamate toxicity. Here, we show that antigen-specific autoimmune T cells, by tailoring the microglial phenotype, can increase the ability of microglia-enriched cultures to remove glutamate. This T-cell-mediated effect could not be achieved by the potent microglia-activating agent lipopolysaccharide (LPS), but was dose-dependently reproduced by the Th1 cytokine interferon (IFN)-γ and significantly reduced by neutralizing anti-IFN-γ antibodies. Under the same conditions, IFN-γ had no effect on cultured astrocytes. Up-regulation of glutamate uptake induced by IFN-γ activation was not accompanied by the acute inflammatory response seen in LPS-activated cultures. These findings suggest that T cells or their cytokines can cause microglia to adopt a phenotype that facilitates rather than impairs glutamate clearance, possibly contributing to restoration of homeostasis. [ABSTRACT FROM AUTHOR]

Adult-onset Niemann-Pick disease type C (NPC) is an infrequent presentation of a rare neurovisceral lysosomal lipid storage disorder caused by autosomal recessive mutations in NPC1 (∼95%) or NPC2 (∼5%). Our patient was diagnosed at age 33 when he presented with a 10-yr history of difficulties in judgment, concentration, speech, and coordination. A history of transient neonatal jaundice and splenomegaly with bone marrow biopsy suggesting a lipid storage disorder pointed to NPC; biochemical ("variant" level cholesterol esterification) and ultrastructural studies in adulthood confirmed the diagnosis. Genetic testing revealed two different missense mutations in the NPC1 gene-V950M and N1156S. Symptoms progressed over >20 yr to severe ataxia and spasticity, dementia, and dysphagia with aspiration leading to death. Brain autopsy revealed mild atrophy of the cerebrum and cerebellum. Microscopic examination showed diffuse gray matter deposition of balloon neurons, mild white matter loss, extensive cerebellar Purkinje cell loss with numerous "empty baskets," and neurofibrillary tangles predominantly in the hippocampal formation and transentorhinal cortex. We performed whole-genome sequencing to examine whether the patient harbored variants outside of the NPC1 locus that could have contributed to his late-onset phenotype. We focused analysis on genetic modifiers in pathways related to lipid metabolism, longevity, and neurodegenerative disease. We identified no rare coding variants in any of the pathways examined nor was the patient enriched for genome-wide association study (GWAS) single-nucleotide polymorphisms (SNPs) associated with longevity or altered lipid metabolism. In light of these findings, this case provides support for the V950M variant being sufficient for adult-onset NPC disease.