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[Display omitted] Type 1 Charcot-Marie-Tooth disease (CMT1) is the most common demyelinating peripheral neuropathy. Patients suffer from progressive muscle weakness and sensory problems. The underlying disease mechanisms of CMT1 are still unclear and no therapy is currently available, hence patients completely rely on supportive care. Balancing protein levels is a complex multistep process fundamental to maintain cells in their healthy state and a disrupted proteostasis is a hallmark of several neurodegenerative diseases. When protein misfolding occurs, protein quality control systems are activated such as chaperones, the lysosomal-autophagy system and proteasomal degradation to ensure proper degradation. However, in pathological circumstances, these mechanisms are overloaded and thereby become inefficient to clear the load of misfolded proteins. Recent evidence strongly indicates that a disbalance in proteostasis plays an important role in several forms of CMT1. In this review, we present an overview of the protein quality control systems, their role in CMT1, and potential treatment strategies to restore proteostasis. [ABSTRACT FROM AUTHOR]

Dental pulp is a highly vascularized and innervated tissue containing a heterogeneous stem cell population with multilineage differentiation potential. Current endodontic treatments focus on the preservation of the pulp tissue and the regeneration of dental pulp after pathological insults. Human dental pulp stem cells (hDPSCs) are currently investigated as stem cell–based therapy for pulp regeneration and for peripheral nerve injury in which neurons and Schwann cells display limited regenerative capacity. We have developed a neuronal differentiation protocol for hDPSCs that requires neurosphere formation before neuronal maturation. Moreover, Schwann cell differentiation of hDPSCs in our group revealed that differentiated hDPSCs have acquired the ability to myelinate and guide neurites from dorsal root ganglia. Besides their dynamic differentiation capacity, hDPSCs were shown to exert a paracrine effect on neural and endothelial cells. Analysis of hDPSC conditioned medium revealed the secretion of a broad spectrum of growth factors including brain-derived neurotrophic factor, nerve growth factor, vascular endothelial growth factor, and glial-derived neurotrophic factor. Application of the conditioned medium to endothelial cells promoted cell migration and tubulogenesis, indicating a paracrine proangiogenic effect. This hypothesis was enforced by the enhanced formation of blood vessels in the chorioallantoic membrane assay in the presence of hDPSCs. In addition, transplantation of 3-dimensional–printed hydroxyapatite scaffolds containing peptide hydrogels and hDPSCs into immunocompromised mice revealed blood vessel ingrowth, pulplike tissue formation, and osteodentin deposition suggesting osteogenic/odontogenic differentiation of hDPSCs. Future studies in our research group will focus on the pulp regeneration capacity of hDPSCs and the role of fibroblasts within the pulp extracellular matrix. [ABSTRACT FROM AUTHOR]

• Microglia are immigrant CNS immune cells that show motility and mobility, especially in the developing brain. • Microglial motility and mobility is likely steered by the constantly changing microenvironment of the CNS. • Microglia populate the developing CNS by proliferation and intensive migration, of which the molecular mechanisms have just started to be unravelled. • Microglia actively participate in CNS development and homeostasis, even at early developmental stages. • Defective microglial functions during development can be related to neurodevelopmental disorders. In the last decade, tremendous progress has been made in understanding the biology of microglia – i.e. the fascinating immigrated resident immune cell population of the central nervous system (CNS). Recent literature reviews have largely dealt with the plentiful functions of microglia in CNS homeostasis, development and pathology, and the influences of sex and the microbiome. In this review, the intriguing aspect of their physical plasticity during CNS development will get specific attention. Microglia move around (mobility) and reshape their processes (motility). Microglial migration into and inside the CNS is most prominent throughout development and consequently most of the data described in this review concern mobility and motility in the changing environment of the developing brain. Here, we first define microglia based on their highly specialized age- and region-dependent gene expression signature and associated functional heterogeneity. Next, we describe their origin, the migration route of immature microglial cells towards the CNS, the mechanisms underlying their invasion of the CNS, and their spatiotemporal localization and surveying behaviour inside the developing CNS. These processes are dependent on microglial mobility and motility which are determined by the microenvironment of the CNS. Therefore, we further zoom in on the changing environment during CNS development. We elaborate on the extracellular matrix and the respective integrin receptors on microglia and we discuss the purinergic and molecular signalling in microglial mobility. In the last section, we discuss the physiological and pathological functions of microglia in which mobility and motility are involved to stress the importance of microglial 'movement'. [ABSTRACT FROM AUTHOR]

Abstract: Spinal cord injury (SCI) is characterized by different phases of inflammatory responses. Increasing evidence indicates that the early chronic phase (two to three weeks after SCI) is characterized by a dramatic invasion of immune cells and a peak of pro-inflammatory cytokine levels, such as tumor necrosis factor-α (TNF-α) derived from the injured spinal cord as well as from injured skin, muscles and bones. However, there is substantial controversy whether these inflammatory processes in later phases lead to pro-regenerative or detrimental effects. In the present study, we investigated whether the inhibition of peripheral TNF-α in the early chronic phase after injury promotes functional recovery in a dorsal hemisection model of SCI. Three different approaches were used to continuously block peripheral TNF-αin vivo, starting 14days after injury. We administered the TNF-α blocker etanercept intraperitoneally (every second day or daily) as well as continuously via osmotic minipumps. None of these administration routes for the TNF-α inhibitor influenced locomotor restoration as assessed by the Basso mouse scale (BMS), nor did they affect coordination and strength as evaluated by the Rotarod test. These data suggest that peripheral TNF-α inhibition may not be an effective therapeutic strategy in the early chronic phase after SCI. [Copyright &y& Elsevier]