The neutrophil extracellular traps in neurological diseases: An update.

Neutrophil extracellular traps released by neutrophils are web-like DNA structures adhered to granulin proteins with bactericidal activity and can be an important mechanism for preventing pathogen dissemination or eliminating microorganisms. However, they also play important roles in diseases of other systems, such as the central nervous system. We tracked the latest advances and performed a review based on published original and review articles related to neutrophil extracellular traps and neurological diseases. Generally, neutrophils barely penetrate the blood-brain barrier into the brain parenchyma, but when pathological changes such as infection, trauma, or neurodegeneration occur, neutrophils rapidly infiltrate the central nervous system to exert their defensive effects. However, neutrophils may adversely affect the host when they uncontrollably release neutrophil extracellular traps upon persistent neuroinflammation. This review focused on recent advances in understanding the mechanisms and effects of neutrophil extracellular traps release in neurological diseases, and we also discuss the role of molecules that regulate neutrophil extracellular traps release in anticipation of clinical applications in neurological diseases.

The Growing Role of Telerehabilitation and Teleassessment in the Management of Movement Disorders in Rare Neurological Diseases: A Scoping Review.

Background: People with rare neurological diseases (RNDs) often experience symptoms related to movement disorders, requiring a multidisciplinary approach, including rehabilitation. Telemedicine applied to rehabilitation and symptom monitoring may be suitable to ensure treatment consistency and personalized intervention. The objective of this scoping review aimed to emphasize the potential role of telerehabilitation and teleassessment in managing movement disorders within RNDs. By providing a systematic overview of the available literature, we sought to highlight potential interventions, outcomes, and critical issues. Methods: A literature search was conducted on PubMed, Google Scholar, IEEE, and Scopus up to March 2024. Two inclusion criteria were followed: (1) papers focusing on telerehabilitation and teleassessment and (2) papers dealing with movement disorders in RNDs. Results: Eighteen papers fulfilled the inclusion criteria. The main interventions were home-based software and training programs, exergames, wearable sensors, smartphone applications, virtual reality and digital music players for telerehabilitation; wearable sensors, mobile applications, and patient home video for teleassessment. Key findings revealed positive outcomes in gait, balance, limb disability, and in remote monitoring. Limitations include small sample sizes, short intervention durations, and the lack of standardized protocols. Conclusion: This review highlighted the potential of telerehabilitation and teleassessment in addressing movement disorders within RNDs. Data indicate that these modalities may play a major role in supporting conventional programs. Addressing limitations through multicenter studies, longer-term follow-ups, and standardized protocols is essential. These measures are essential for improving remote rehabilitation and assessment, contributing to an improved quality of life for people with RNDs.

Research advances in huntingtin-associated protein 1 and its application prospects in diseases.

Huntingtin-associated protein 1 (HAP1) was the first protein discovered to interact with huntingtin. Besides brain, HAP1 is also expressed in the spinal cord, dorsal root ganglion, endocrine, and digestive systems. HAP1 has diverse functions involving in vesicular transport, receptor recycling, gene transcription, and signal transduction. HAP1 is strongly linked to several neurological diseases, including Huntington's disease, Alzheimer's disease, epilepsy, ischemic stroke, and depression. In addition, HAP1 has been proved to participate in cancers and diabetes mellitus. This article provides an overview of HAP1 regarding the tissue distribution, cell localization, functions, and offers fresh perspectives to investigate its role in diseases.

Association between serum neurofilament light chains (sNfL) and neurologic disorders in a representative sample of US adults: a cross-sectional study.

BACKGROUND: While increased neurofilament light chain (NfL) in serum concentrations are linked to the progression of several neurological conditions, their distribution and implications within the general adult population remain largely unexplored. The current research aims to clarify the relationship among serum NfL levels and neurological disorders in a broad and representative population sample. METHODS: We utilized information gathered from 1,751 adults involved in the 2013-2014 cycle of the National Health and Nutrition Examination Survey (NHANES). Our analytical approach encompassed logistic regression, smoothed curve fitting, and subgroup analyses to identify potential correlations between serum NfL levels and neurological conditions, including depression, severe hearing and visual impairments, stroke, subjective memory deficits, and sleep problems. RESULTS: After adjusting for confounders, we found that higher serum NfL concentrations were significantly associated with increased risks of depression, stroke, subjective memory deficits, and longer sleep duration (p < 0.05). Subgroup analyses supported these findings. Additionally, BMI significantly influenced the relationship between serum NfL levels and subjective memory deficits. CONCLUSION: Our research shows that higher serum NfL levels are strongly related to an elevated risk for several neurological disorders. These findings highlight the role of serum NfL serving as a critical marker for early detection and monitoring of neurological conditions, emphasizing its importance in both clinical and public health settings.

The use of digital tools in rare neurological diseases towards a new care model: a narrative review.

Rare neurological diseases as a whole share peculiar features as motor and/or cognitive impairment, an elevated disability burden, a frequently chronic course and, in present times, scarcity of therapeutic options. The rarity of those conditions hampers both the identification of significant prognostic outcome measures, and the development of novel therapeutic approaches and clinical trials. Collection of objective clinical data through digital devices can support diagnosis, care, and therapeutic research. We provide an overview on recent developments in the field of digital tools applied to rare neurological diseases, both in the care setting and as providers of outcome measures in clinical trials in a representative subgroup of conditions, including ataxias, hereditary spastic paraplegias, motoneuron diseases and myopathies.

[Application of peripheral magnetic stimulation in physiotherapeutic practice. (A literature review)]. / Primenenie perifericheskoi magnitnoi stimulyatsii v fizioterapevticheskoi praktike. (Obzor literatury).

Search and development of new physiotherapeutic technologies of regenerative medicine for the treatment of patients with different diseases is an urgent task of modern medicine. OBJECTIVE: To analyze scientific data on the effectiveness of the peripheral magnetic stimulation (PMS) application in patients with different diseases. MATERIAL AND METHODS: An analysis of publications in databases of electronic resources (PEDro, PubMed, Embase, eLibrary, Cochrane Library) over the past 20 years was carried out, the results of PMS application in patients with different nosologies were presented. RESULTS: The majority of the presented articles confirm the clinical effectiveness of PMS application mainly in patients with diseases of the nervous system, spine and genitourinary system. CONCLUSION: Further research to confirm the effectiveness of the therapeutic impact of magnetic stimulation in patients with other nosologies is needed.

Analysis of sleep apnea research with a special focus on the use of positron emission tomography as a study tool.

The quality of sleep plays a significant role in determining human well-being, and studying sleep and sleep disorders using various methods can aid in the prevention and treatment of diseases. Positron emission tomography (PET) is a noninvasive and highly sensitive medical imaging technique that has been widely adopted in the clinic. This review article provides data on research activity related to sleep and sleep apnea and discusses the use of PET in investigating sleep apnea and other sleep disorders. We conducted a statistical analysis of the number of original research articles published on sleep and sleep apnea between 1965 and 2021 and found that there has been a dramatic increase in publications since 1990. The distribution of contributing countries and regions has also undergone significant changes. Although there is an extensive body of literature on sleep research (256,399 original research articles during 1965-2021), PET has only been used in 54 of these published studies, indicating a largely untapped area of research. Nonetheless, PET is a useful tool for identifying connections between sleep disorders and pathological changes in various diseases, including neurological, metabolic, and cardiovascular disorders, as well as cancer. To facilitate the broader use of PET in sleep apnea research, further studies are needed in both clinical and preclinical settings.

Half-Curcuminoids Encapsulated in Alginate-Glucosamine Hydrogel Matrices as Bioactive Delivery Systems.

The therapeutic effects of curcumin and its derivatives, based on research in recent years, are limited by their low bioavailability. To improve bioavailability and develop the medical field of application, different delivery systems have been developed that are adapted to certain environments or the proposed target type. This study presents some half-curcuminoids prepared by the condensation of acetylacetone with 4-hydroxybenzaldehyde (C1), 4-hydroxy-3-methoxybenzaldehyde (C2), 4-acetamidobenzaldehyde (C3), or 4-diethylaminobenzaldehyde (C4), at microwaves as a simple, solvent-free, and eco-friendly method. The four compounds obtained were characterized in terms of morphostructural and photophysical properties. Following the predictions of theoretical studies on the biological activities related to the molecular structure, in vitro tests were performed for compounds C1-C3 to evaluate the antitumor properties and for C4's possible applications in the treatment of neurological diseases. The four compounds were encapsulated in two types of hydrogel matrices. First, the alginate-glucosamine network was generated and then the curcumin analogs were loaded (G1, G3, G5-G7, and G9). The second type of hydrogels was obtained by loading the active compound together with the generation of the hydrogel carrier matrices, by simply dissolving (G4 and G10) or by chemically binding half-curcuminoid derivatives to glucosamine (G2 and G8). Thus, two types of curcumin analog delivery systems were obtained, which could be applied in various types of medical treatments.

Mechanisms of cuproptosis and its relevance to distinct diseases.

Copper is a trace element required by the organism, but once the level of copper exceeds the threshold, it becomes toxic and even causes death. The underlying mechanisms of copper-induced death are inconclusive, with different studies showing different opinions on the mechanism of copper-induced death. Multiple investigations have shown that copper induces oxidative stress, endoplasmic reticulum stress, nucleolar stress, and proteasome inhibition, all of which can result in cell death. The latest research elucidates a copper-dependent death and denominates it as cuproptosis. Cuproptosis takes place through the combination of copper and lipoylated proteins of the tricarboxylic acid cycle, triggering agglomeration of lipoylated proteins and loss of iron-sulfur cluster proteins, leading to proteotoxic stress and ultimately death. Given the toxicity and necessity of copper, abnormal levels of copper lead to diseases such as neurological diseases and cancer. The development of cancer has a high demand for copper, neurological diseases involve the change of copper contents and the binding of copper to proteins. There is a close relationship between these two kinds of diseases and copper. Here, we summarize the mechanisms of copper-related death, and the association between copper and diseases, to better figure out the influence of copper in cell death and diseases, thus advancing the clinical remedy of these diseases.

Adeno-associated virus vector delivery to the brain: Technology advancements and clinical applications.

Adeno-associated virus (AAV) vectors have emerged as a promising tool in the development of gene therapies for various neurological diseases, including Alzheimer's disease and Parkinson's disease. However, the blood-brain barrier (BBB) poses a significant challenge to successfully delivering AAV vectors to the brain. Strategies that can overcome the BBB to improve the AAV delivery efficiency to the brain are essential to successful brain-targeted gene therapy. This review provides an overview of existing strategies employed for AAV delivery to the brain, including direct intraparenchymal injection, intra-cerebral spinal fluid injection, intranasal delivery, and intravenous injection of BBB-permeable AAVs. Focused ultrasound has emerged as a promising technology for the noninvasive and spatially targeted delivery of AAV administered by intravenous injection. This review also summarizes each strategy's current preclinical and clinical applications in treating neurological diseases. Moreover, this review includes a detailed discussion of the recent advances in the emerging focused ultrasound-mediated AAV delivery. Understanding the state-of-the-art of these gene delivery approaches is critical for future technology development to fulfill the great promise of AAV in neurological disease treatment.

Human Stem Cells in Regenerative Medicine.

Modern medicine now has the capacity to improve therapy for many human diseases by introducing adult somatic stem cells that can repair or replace defective or damaged tissues. However, the area is still in an early phase of development, so all new applications must be carefully designed for maximal safety as well as effectiveness.

MSC-Based Cell Therapy in Neurological Diseases: A Concise Review of the Literature in Pre-Clinical and Clinical Research.

Mesenchymal stem cells (MSCs) are multipotent stromal cells with the ability to self-renew and multi-directional differentiation potential. Exogenously administered MSCs can migrate to damaged tissue sites and participate in the repair of damaged tissues. A large number of pre-clinical studies and clinical trials have demonstrated that MSCs have the potential to treat the abnormalities of congenital nervous system and neurodegenerative diseases. Therefore, MSCs hold great promise in the treatment of neurological diseases. Here, we summarize and highlight current progress in the understanding of the underlying mechanisms and strategies of MSC application in neurological diseases.

Exploring the physiological role of the G protein-coupled estrogen receptor (GPER) and its associations with human diseases.

Estrogen is a group of hormones that collaborate with the nervous system to impact the overall well-being of all genders. It influences many processes, including those occurring in the central nervous system, affecting learning and memory, and playing roles in neurodegenerative diseases and mental disorders. The hormone's action is mediated by specific receptors. Significant roles of classical estrogen receptors, ERα and ERß, in various diseases were known since many years, but after identifying a structurally and locationally distinct receptor, the G protein-coupled estrogen receptor (GPER), its role in human physiology and pathophysiology was investigated. This review compiles GPER-related information, highlighting its impact on homeostasis and diseases, while putting special attention on functions and dysfunctions of this receptor in neurobiology and biobehavioral processes. Understanding the receptor modulation possibilities is essential for therapy, as disruptions in receptors can lead to diseases or disorders, irrespective of correct estrogen levels. We conclude that studies on the GPER receptor have the potential to develop therapies that regulate estrogen and positively impact human health.

Soft bioelectronics for diagnostic and therapeutic applications in neurological diseases.

Physical and chemical signals in the central nervous system yield crucial information that is clinically relevant under both physiological and pathological conditions. The emerging field of bioelectronics focuses on the monitoring and manipulation of neurophysiological signals with high spatiotemporal resolution and minimal invasiveness. Significant advances have been realized through innovations in materials and structural design, which have markedly enhanced mechanical and electrical properties, biocompatibility, and overall device performance. The diagnostic and therapeutic potential of soft bioelectronics has been corroborated across a diverse array of pre-clinical settings. This review summarizes recent studies that underscore the developments and applications of soft bioelectronics in neurological disorders, including neuromonitoring, neuromodulation, tumor treatment, and biosensing. Limitations and outlooks of soft devices are also discussed in terms of power supply, wireless control, biocompatibility, and the integration of artificial intelligence. This review highlights the potential of soft bioelectronics as a future platform to promote deciphering brain functions and clinical outcomes of neurological diseases.

Pharmacotherapeutic potential of Vitis vinifera(grape) in age-related neurological diseases / Potencial farmacoterapéutico de Vitis vinifera(uva) en enfermedades neurológicas asociadas a la edad

Age-related neurological disorders (ANDs), including neurodegenerative diseases, are complex illnesses with an increasing risk with advancing years. The central nervous system's neuropathological conditions, including oxidative stress, neuroinflammation, and protein misfolding, are what define ANDs. Due to the rise in age-dependent prevalence, efforts have been made to combat ANDs. Vitis viniferahas a long history of usageto treat a variety of illness symptoms. Because multiple ligand sites may be targeted, Vitis viniferacomponents can be employed to treat ANDs. This is demonstrated by the link between the structure and action of these compounds. This review demonstrates that Vitis viniferaand its constituents, including flavonoids, phenolic compounds, stilbenoidsandaromatic acids, are effective at reducing the neurological symptoms and pathological conditions of ANDs. This is done by acting as an antioxidant and anti-inflammatory. The active Vitis vinifera ingredients have therapeutic effects on ANDs, as this review explains.

Las enfermedades neurológicas asociadas a la edad (AND, por su sigla en inglés) incluyendo las enfermedades neurodegenerativas, son enfermedades complejas con un riesgo creciente con la edad. Las condiciones neuropatológicas del sistema nervioso central, que incluyen el estrés oxidativo, la neuro inflamación, y el plegado erróneo de proteínas, son lo que define las AND. Debido al aumento en la prevalencia dependiente de la edad, se han hecho esfuerzos para combatir las AND. Vitis vinifera tiene una larga historia de uso para el tratamiento de síntomas. Puesto que puede hacer objetivo a muchos sitios ligando, los componentes de Vitis viniferase pueden utilizar para tratar AND. Esto se demuestra por el vínculo entre la estructura y la acción de estos compuestos. Esta revisión demuestra que la Vitis viniferay sus constituyentes, incluídos los flavonoides, componentes fenólicos, estilbenoides, y ácidos aromáticos, son efectivos para reducir los síntomas neurológicos y las condiciones patológicas de AND. Esto se produce por su acción como antioxidante y antiinflamatorio. Los ingredientes activos de Vitis vinifera tienen efectos terapéuticos en AND, y esta revisión lo explica.

Advancements in Single-Cell RNA Sequencing Research for Neurological Diseases.

Neurological diseases are a major cause of the global burden of disease. Although the mechanisms of the occurrence and development of neurological diseases are not fully clear, most of them are associated with cells mediating neuroinflammation. Yet medications and other therapeutic options to improve treatment are still very limited. Single-cell RNA sequencing (scRNA-seq), as a delightfully potent breakthrough technology, not only identifies various cell types and response states but also uncovers cell-specific gene expression changes, gene regulatory networks, intercellular communication, and cellular movement trajectories, among others, in different cell types. In this review, we describe the technology of scRNA-seq in detail and discuss and summarize the application of scRNA-seq in exploring neurological diseases, elaborating the corresponding specific mechanisms of the diseases as well as providing a reliable basis for new therapeutic approaches. Finally, we affirm that scRNA-seq promotes the development of the neuroscience field and enables us to have a deeper cellular understanding of neurological diseases in the future, which provides strong support for the treatment of neurological diseases and the improvement of patients' prognosis.

Toward diffusion tensor imaging as a biomarker in neurodegenerative diseases: technical considerations to optimize recordings and data processing.

Neuroimaging biomarkers have shown high potential to map the disease processes in the application to neurodegenerative diseases (NDD), e.g., diffusion tensor imaging (DTI). For DTI, the implementation of a standardized scanning and analysis cascade in clinical trials has potential to be further optimized. Over the last few years, various approaches to improve DTI applications to NDD have been developed. The core issue of this review was to address considerations and limitations of DTI in NDD: we discuss suggestions for improvements of DTI applications to NDD. Based on this technical approach, a set of recommendations was proposed for a standardized DTI scan protocol and an analysis cascade of DTI data pre-and postprocessing and statistical analysis. In summary, considering advantages and limitations of the DTI in NDD we suggest improvements for a standardized framework for a DTI-based protocol to be applied to future imaging studies in NDD, towards the goal to proceed to establish DTI as a biomarker in clinical trials in neurodegeneration.

Transcytosis-Driven Treatment of Neurodegenerative Disorders by mRNA-Expressed Antibody-Transferrin Conjugates.

The recent setbacks in the withdrawal and approval delays of antibody treatments of neurodegenerative disorders (NDs), attributed to their poor entry across the blood-brain barrier (BBB), emphasize the need to bring novel approaches to enhance the entry across the BBB. One such approach is conjugating the antibodies that bind brain proteins responsible for NDs with the transferrin molecule. This glycoprotein transports iron into cells, connecting with the transferrin receptors (TfRs), piggybacking an antibody-transferrin complex that can subsequently release the antibody in the brain or stay connected while letting the antibody bind. This process increases the concentration of antibodies in the brain, enhancing therapeutic efficacy with targeted delivery and minimum systemic side effects. Currently, this approach is experimented with using drug-transferring conjugates assembled in vitro. Still, a more efficient and safer alternative is to express the conjugate using mRNA technology, as detailed in this paper. This approach will expedite safer discoveries that can be made available at a much lower cost than the recombinant process with in vitro conjugation. Most importantly, the recommendations made in this paper may save the antibodies against the NDs that seem to be failing despite their regulatory approvals.