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In this study, we investigated a deleterious mutation in the β-xylosidase gene, xylA (AkxylA), in Aspergillus luchuensis mut. kawachii IFO 4308 by constructing an AkxylA disruptant and complementation strains of AkxylA and xylA derived from A. luchuensis RIB2604 (AlxylA), which does not harbor the mutation in xylA. Only the AlxylA complementation strain exhibited significantly higher growth and substantial β-xylosidase activity in medium containing xylan, accompanied by an increase in XylA expression...

Brain-derived neurotrophic factor (BDNF) is a neurotrophic protein that promotes neuronal survival, increases neurotransmitter synthesis, and has potential therapeutic effects in neurodegenerative and psychiatric diseases, but its drug development has been limited by the fact that recombinant proteins of BDNF are unstable and do not penetrate the blood-brain barrier (BBB). In this study, we fused a TAT membrane-penetrating peptide with BDNF to express a recombinant protein (TBDNF), which was then PEG-modified to P-TBDNF...

Infection with Plasmodium falciparum is often deadly when it results in cerebral malaria, which is associated with neuropathology described as an overwhelming inflammatory response and mechanical obstruction of cerebral microvascular. PI3Kγ is a critical component of intracellular signal transduction and plays a central role in regulating cell chemotaxis, migration, and activation. The purpose of this study was to examine the relationship between inhibiting the PI3Kγ pathway and the outcome of experimental cerebral malaria (ECM) in C57BL/6J mice infected with the mouse malaria parasite, Plasmodium berghei ANKA...

Glioblastoma (GBM) is the highest grade of glioma for which no effective therapy is currently available. Despite extensive research in diagnosis and therapy, there has been no significant improvement in GBM outcomes, with a median overall survival continuing at a dismal 15-18 months. In recent times, glioblastoma stem cells (GSCs) have been identified as crucial drivers of treatment resistance and tumor recurrence, and GBM therapies targeting GSCs are expected to improve patient outcomes. We used a multistep in silico screening strategy to identify repurposed candidate drugs against selected therapeutic molecular targets in GBM with potential to concomitantly target GSCs...

The blood-brain barrier (BBB) plays a critical role in regulating the exchange of substances between peripheral blood and the central nervous system and in maintaining the stability of the neurovascular unit in neurological diseases. To guide clinical treatment and basic research on BBB protection following brain injury, this manuscript reviews how BBB disruption develops and influences neural recovery after stroke and traumatic brain injury (TBI). By summarizing the pathological mechanisms of BBB damage, we underscore the critical role of promoting BBB repair in managing brain injury...

Cerebral malaria (CM) is a severe complication of Plasmodium falciparum (P. falciparum) infection, with complex pathogenesis involving multiple factors, including the host's immunological response. T lymphocytes, specifically CD4+ T helper cells and CD8+ cytotoxic T cells, are crucial in controlling parasite growth and activating cells for parasite clearance via cytokine secretion. Contrary to this, reports also suggest the pathogenic nature of T lymphocytes as they are often involved in disease progression and severity...

Gaucher disease (GD), a rare hereditary lysosomal storage disorder, occurs due to a deficiency in the enzyme β-glucocerebrosidase (GCase). This deficiency leads to the buildup of substrate glucosylceramide (GlcCer) in macrophages, eventually resulting in various complications. Among its three types, GD2 is particularly severe with neurological involvements. Current treatments, such as enzyme replacement therapy (ERT), are not effective for GD2 and GD3 due to their inability to cross the blood-brain barrier (BBB)...

BACKGROUND AND PURPOSE: The purpose of this study is to evaluate the feasibility of using 3-dimensional (3D) ultra-short echo time (UTE) radial imaging method for measurement of the permeability of the blood-brain barrier (BBB) to gadolinium-based contrast agent. In this study, we propose to use the golden-angle radial sparse parallel (GRASP) method with 3D center-out trajectories for UTE, hence named as 3D UTE-GRASP. We first examined the feasibility of using 3D UTE-GRASP dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) for differentiating subtle BBB disruptions induced by focused ultrasound (FUS)...

Iron oxide nanoparticles (IONPs) are considered as the most biocompatible magnetic materials suitable for biomedical applications. Nevertheless, there are many evidences of their toxicity for living organisms and partially neurotoxicity. The central nervous system is protected from undesirable substances circulating in the bloodstream by the blood-brain barrier (BBB). And even if being small enough, some nanoparticles could be able to penetrate cell membranes in other cells but will often be delayed by the BBB cells...

Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease, and it is characterized by the intracellular and extracellular accumulation of α-synuclein (α-syn) and Tau, which are major components of cytosolic protein inclusions called Lewy bodies, in the brain. Currently, there is a lack of effective methods that preventing PD progression. It has been suggested that the plasminogen activation system, which is a major extracellular proteolysis system, is involved in PD pathogenesis...

Gliomas are among the most fatal tumors, and the available therapeutic options are very limited. Additionally, the blood-brain barrier (BBB) prevents most drugs from entering the brain. We designed and produced a ferritin-based stimuli-sensitive nanocarrier with high biocompatibility and water solubility. It can incorporate high amounts of the potent topoisomerase 1 inhibitor Genz-644282. Here, we show that this nanocarrier, named The-0504, can cross the BBB and specifically deliver the payload to gliomas that express high amounts of the ferritin/transferrin receptor TfR1 (CD71)...

The administration of promising medications for the treatment of neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) is significantly hampered by the blood-brain barrier (BBB). Nanotechnology has recently come to light as a viable strategy for overcoming this obstacle and improving drug delivery to the brain. With a focus on current developments and prospects, this review article examines the use of nanoparticles to overcome the BBB constraints to improve drug therapy for AD The potential for several nanoparticle-based approaches, such as those utilizing lipid-based, polymeric, and inorganic nanoparticles, to enhance drug transport across the BBB are highlighted...

Bupivacaine (BUP) is an anesthetic commonly used in clinical practice that when used for spinal anesthesia, might exert neurotoxic effects. Thioredoxin-interacting protein (TXNIP) is a member of the α-arrestin protein superfamily that binds covalently to thioredoxin (TRX) to inhibit its function, leading to increased oxidative stress and activation of apoptosis. The role of TXNIP in BUP-induced oxidative stress and apoptosis remains to be elucidated. In this context, the present study aimed to explore the effects of TXNIP knockdown on BUP-induced oxidative stress and apoptosis in the spinal cord of rats and in PC12 cells through the transfection of adeno-associated virus-TXNIP short hairpin RNA (AAV-TXNIP shRNA) and siRNA-TXNIP, respectively...

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of commonly targeted receptors. Unspecific chemotherapy is currently the main therapeutic option, with poor results. Another major challenge is the frequent appearance of brain metastasis (BM) associated with a significant decrease in patient overall survival. The treatment of BM is even more challenging due to the presence of the blood-brain barrier (BBB). Here, we present a dual-acting peptide (PepH3-vCPP2319) designed to tackle TNBC/BM, in which a TNBC-specific anticancer peptide (ACP) motif (vCPP2319) is joined to a BBB peptide shuttle (BBBpS) motif (PepH3)...

Multiple sclerosis (MS), traditionally perceived as a neurodegenerative disease, exhibits significant vascular alternations, including blood-brain barrier (BBB) disruption, which may predispose patients to increased cardiovascular risks. This vascular dysfunction is intricately linked with the infiltration of immune cells into the central nervous system (CNS), which plays a significant role in perpetuating neuroinflammation. Additionally, oxidative stress serves not only as a byproduct of inflammatory processes but also as an active contributor to neural damage...

Spinal cord injury (SCI) presents a complex challenge in neurorehabilitation, demanding innovative therapeutic strategies to facilitate functional recovery. This study investigates the effects of treadmill training on SCI recovery, emphasizing motor function enhancement, neural tissue preservation, and axonal growth. Our research, conducted on a rat model, demonstrates that controlled treadmill exercises significantly improve motor functions post-SCI, as evidenced by improved scores on the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and enhanced electromyography readings...

This review article focuses on the upstream pertinent pathophysiology leading to neurodegenerative disease. Specifically, the nexus appears to be blood-brain barrier (BBB) leakiness resulting in a two-prong inflammatory disease spectrum damaging the microvasculature and corrupting protein synthesis and degradation with accumulating misfolded toxic proteins. The suboptimal results of removing misfolded proteins mean a new approach to disease in the preclinical state is required aimed at other targets. Validated noninvasive imaging and serologic biomarkers of early preclinical disease implemented in the high-risk patient cohort along with periodic surveillance once effective treatments are developed will be required...

Neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis epitomize a class of insidious and relentless neurological conditions that are difficult to cure. Conventional therapeutic regimens often fail due to the late onset of symptoms, which occurs well after irreversible neurodegeneration has begun. The integrity of the blood-brain barrier (BBB) further impedes efficacious drug delivery to the central nervous system, presenting a formidable challenge in the pharmacological treatment of NDDs...

The impairment of the blood-brain barrier (BBB) has been increasingly recognised as a critical element in the early pathogenesis of Alzheimer's disease (AD), prompting a focus on brain endothelial cells (BECs), which serve as the primary constituents of the BBB. Death receptor 6 (DR6) is highly expressed in brain vasculature and acts downstream of the Wnt/β-catenin pathway to promote BBB formation during development. Here, we found that brain endothelial DR6 levels were significantly reduced in a murine model of AD (APPswe /PS1dE9 mice) at the onset of amyloid-β (Aβ) accumulation...

Given the widespread production and use of plastics, poor biodegradability, and inadequate recycling, micro/nanoplastics (MNPs) have caused widespread environmental pollution. As a result, humans inevitably ingest MNPs through various pathways. However, there is still no consensus on whether exposure to MNPs has adverse effects on humans. This article aims to provide a comprehensive overview of the knowledge of MNPs and the potential mechanisms of their impact on the central nervous system. Numerous in vivo and in vitro studies have shown that exposure to MNPs may pass through the blood-brain barrier (BBB) and lead to neurotoxicity through impairments in oxidative and inflammatory balance, neurotransmitter alternation, nerve conduction-related key enzymes, and impact through the gut-brain axis...