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Polysaccharide-based nanoparticles offer significant potential for the treatment of neurodegenerative diseases and the modulation of inflammatory responses in the central nervous system. These biopolymers, when derived from natural sources, possess inherent immunomodulatory properties, which can be leveraged to regulate immune activity, positioning them as promising candidates for both prophylactic and therapeutic strategies. Furthermore, when integrated with other materials, polysaccharides form nanocomposites with enhanced structural, physicochemical, and biological properties, making them highly versatile platforms for drug delivery in the central nervous system. This review provides a comprehensive analysis of polysaccharide-based nanoparticles, focusing on their application in the treatment of three major neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Emphasis is placed on optimizing these nanomaterials for targeted drug delivery and immune modulation, underscoring their potential to improve therapeutic outcomes in neurodegenerative disorders. The review also examines the structural, chemical, and biological characteristics of key polysaccharides, and explores their innovative roles in combating neuroinflammation and neurodegeneration.

Brain cancer, with glioblastoma (GBM) being one of the most aggressive and treatment-resistant cancers, represents a leading cause of mortality and morbidity worldwide. Its complex nature and the presence of the blood-brain barrier (BBB) significantly hinder the effectiveness of conventional therapies, posing major challenges for treatment development. In this context, nanotechnology—particularly nanomedicine—has emerged as a promising strategy to overcome these barriers and enhance standard treatments like chemotherapy and radiotherapy (RT). This review focuses on three of the most challenging brain neoplasms—GBM, brain metastases, and pediatric brain tumors—and explores the growing role of nanoparticle-based therapies, with special emphasis on gold nanoparticles (AuNPs). Owing to their unique physicochemical properties, such as surface functionalization, biocompatibility, and the ability to cross the BBB, AuNPs have shown great potential in selectively delivering drugs, enhancing RT as radiosensitizers, and reducing systemic toxicity. Despite their therapeutic advantages, concerns remain regarding the long-term safety of AuNPs. Their small size and ability to cross biological barriers may lead to unintended biodistribution, immune responses, and cytotoxic effects. Reported risks include inflammatory reactions, apoptosis, and developmental toxicity, highlighting the need for comprehensive safety assessments. AuNPs offer a promising avenue for improving therapeutic efficacy and patient survival in brain cancers. However, their clinical application requires further in-depth preclinical and clinical evaluation to ensure both effectiveness and safety

Alzheimer's disease (AD), a neurodegenerative disease leading to dementia, lacks a single definitive diagnosis. While current medications only manage symptoms, the ideal treatment would restore cognition. Traditional therapies targeting beta-amyloid haven't yielded significant results, while new approaches target tau protein tangles, protein degradation pathways, inflammation, and neurotrophic factor depletion. Autophagy, a cellular degradation and recycling process, has emerged as a crucial hallmark and contributor to the pathogenesis of AD. Notably, autophagy induction has emerged as a promising therapeutic approach, with inducers like celastrol and caudatin promoting the degradation of toxic protein aggregates. Additionally, innovative drug formulations, such as nanoparticles, are being explored for targeted drug delivery. Research is increasingly focusing on neuroinflammation and developing multi-targeted drugs to address various aspects of AD, potentially leading to preventive strategies in the early stages. This review summarizes the current state and emerging trends in AD drug development.

Neurodegenerative diseases (NDs) are disorders that drastically alter the physiological functioning of neurons in the brain. These processes are often accompanied by abnormal protein aggregates that alter the physical and chemical properties of brain tissue and peripheral nerves. The causes of NDs are complex, involving genetic factors, neuroinflammation, oxidative stress, environmental influences, and lifestyle, while symptoms and progression vary significantly based on the mechanisms of cell death. Currently, no definitive treatment exists for NDs, as the underlying degenerative processes remain poorly understood. Existing therapies focus on symptom alleviation but are insufficient to halt or prevent disease progression. This highlights the urgent need for strategies that mimic the pathophysiology of NDs, facilitating deeper insights and the development of effective treatments. Conventional in vitro and in vivo models attempt to replicate NDs but often fail to capture the physiological complexity of nervous tissue and its interactions. In this context, 3D microfluidic bioprinting emerges as a transformative technology. By enabling precise deposition of cells and biomaterials, it allows the creation of in vitro models with a high degree of structural and functional complexity. These advancements provide a valuable platform for faithfully modeling NDs, bridging critical gaps in our understanding, and paving the way toward innovative therapeutic approaches.

Iron accumulation in the prefrontal cortex (PFC) has been implicated in neurodegeneration and cognitive decline. Magnetic resonance imaging (MRI) enables noninvasive quantification of brain iron content and deposition. This review aimed to summarize the evidence on the MRI-based assessment of PFC iron accumulation in healthy individuals and patients with neurodegeneration. A systematic preliminary literature review was conducted using the PubMed, Scopus, Web of Science, and Embase databases. MRI techniques for capturing susceptibility changes reflecting iron, such as susceptibility-weighted imaging (SWI), quantitative susceptibility mapping (QSM), and R2* mapping, were included. Data were extracted, and narrative synthesis was performed. Twelve studies that measured PFC iron levels using MRI in diseases with neurodegeneration (five studies) and healthy subjects (seven studies) were included. In general, studies involving diseases with neurodegeneration have found that increased PFC iron content correlates with cognitive impairment. Aging studies on healthy subjects have reported that age-related accumulation of PFC iron, particularly in the dorsolateral, medial, and anterior subregions, increases with age, and is associated with reduced dopamine signaling and poorer cognition. MRI techniques, such as QSM, can quantify prefrontal iron accumulation in diseases with neurodegeneration and aging. As imaging biomarkers, increased prefrontal iron levels may contribute to neurodegeneration and cognitive decline. Longitudinal studies combining advanced QSM and other advanced neuroimaging techniques with cognitive assessments may further elucidate the effects of iron dysregulation on PFC function. Thus, our findings highlight the importance of MRI as a sensitive tool for assessing PFC iron content and its potential role in understanding the pathogenesis of neurodegeneration and the effects of aging on the brain.

Several noninvasive brain stimulation techniques have gained significant attention in neurocognitive science and clinical research due to their potential efficacy in addressing neurological, psychiatric, and cognitive impairments. This study explores global trends and research hotspots in brain stimulation research for cognitive impairment and related disorders. Using a data set from 1989 to 2024 sourced from the Web of Science Core Collection, 4156 records were analyzed through bibliometric methods, including publication trends, country or region, and institutional analysis, and document co-citation analysis (DCA). Results revealed a steady increase in research, with a significant increase in publications during the period from 2019 to 2023. The USA led in citation counts (1117), centrality (0.37), while China topped the burst value (72.31). The University of London led in citation counts (235), whereas Capital Medical University topped the sigma value (1.77). Transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS) dominated the top positions in DCA analysis. Emerging trends were identified through burst keywords, including “transcranial Doppler,” “subthalamic nucleus stimulation,” “cerebral blood flow,” “vascular dementia,” and “cardiopulmonary bypass.” These emerging research hotspots underscore the growing focus on vascular aspects of cognitive impairment and advanced brain stimulation methods. Additionally, newer noninvasive techniques like fast gamma magnetic stimulation, paired-associative stimulation with TMS (PAS-TMS), and theta-burst stimulation are identified as promising avenues for future research, offering significant potential for therapeutic advancements. This study provides a comprehensive overview of the global landscape, trends, and future directions in brain stimulation research for cognitive impairment.

The aggregation of β-amyloid (Aβ) peptides has been associated with the onset of Alzheimer's disease (AD) by causing neurotoxicity due to oxidative stress and apoptosis. Cordycepin is a natural derivative of the nucleoside adenosine that displays potent antioxidant, antitumor, anti-inflammatory, and neuroprotective properties. However, the mechanism of the neuroprotective effect of cordycepin toward Aβ-induced neurotoxicity, as well as underlying mechanisms, is still unclear. In this study, we found that cordycepin conferred neuroprotection to catecholaminergic PC12 neuronal cell cultures exposed to Aβ_1–42-insult by reducing the production of reactive oxygen species, restoring the mitochondrial membrane potential, and inhibiting apoptosis. Cordycepin stimulated the phosphorylation of extracellular signal-regulated kinase (ERK) and cyclic AMP-responsive element-binding protein (CREB) in a time- and concentration-dependent manner. Inhibition of the ERK pathway reduced the neuroprotective effect of cordycepin. Similar results were obtained with hippocampal HT22 neuronal cell cultures. Cumulatively, these findings suggest that cordycepin-induced neuroprotection toward Aβ_1–42 neurotoxic insult may involve activation of the ERK/CREB pathway. This study expands our knowledge of the neuroprotective function of cordycepin and suggests that it holds promise as a natural lead compound for drug development in AD.

This study aims to investigate the relationship between Parkinson's disease (PD) and colorectal cancer (CRC) risk by a systematic review and meta-analysis. Using Embase, Pubmed, and Cochrane Library databases, 21 articles reporting clinical data of 1,635,873 PD patients and 10,388,842 healthy individuals were finally included. Based on the results of pooled analysis, we found that PD patients exhibited a decreased risk of CRC (relative risk (RR) = 0.74; 95% confidence interval (CI), 0.68–0.80). In contrast to case-control (RR = 0.80; 95% CI, 0.64–1) and cohort studies (RR = 0.72; 95% CI, 0.66–0.79), the combined risk of PD patients with CRC in Asian nations (RR = 0.67; 95% CI, 0.58–0.78) was lower than that in Western countries (RR = 0.76; 95% CI, 0.70–0.82). In comparison to rectal cancer (RR = 0.82; 95% CI, 0.69–0.97), PD patients exhibited a lower combined risk of colon cancer (RR = 0.76; 95% CI, 0.67–0.86). Furthermore, the combined CRC risks for patients in studies published before 2010 and after 2010 were 0.76 (RR = 0.76; 95% CI, 0.66–0.88) and 0.74 (RR = 0.74; 95% CI, 0.68–0.80), respectively. These findings indicate that patients with PD had a reduced risk of CRC. Future studies are merited in exploring pathological molecular linkages or underlying mechanisms of inverse association between CRC and PD.

This study aimed to investigate the causal relationship between systemic lupus erythematosus (SLE) and juvenile myoclonic epilepsy (JME). Univariable and reverse Mendelian randomization (MR) analyses were performed to investigate the potential causal associations between SLE, systemic autoimmune disorders (SADs), and JME. Two-step mediation MR analysis was further performed to explore indirect factors that may influence the relationship between SLE and JME. Summary data on SADs were extracted from the Integrative Epidemiology Unit Open genome-wide association study database, and summary statistics for JME were acquired from the International League Against Epilepsy Consortium. The inverse-variance weighted (IVW) method was used for primary analysis, supplemented by MR-Egger and weighted median. In the univariable MR analysis, IVW results indicated a causal relationship between SLE and an increased risk of JME (odds ratio = 1.0030, 95% confidence interval, 1.0004–1.0057; p = 0.023). The subsequent mediation MR analysis showed that inflammatory cytokines may not be the mediating factors between SLE and JME, while the inverse MR analysis found no significant relationship. Our study indicated that genetic susceptibility to SLE was causally linked to JME. However, subsequent mediation analysis failed to identify the potential mediators that could influence this relationship. Moreover, evidence suggested that other SADs were not causally associated with JME. This study may provide guidance for screening risk factors for seizures and exploring potential treatments in SLE and JME, and even all SADs and JME.

Parkinson's disease (PD) is a neurodegenerative disease characterized by degeneration of dopamine neurons in the substantia nigra pars compacta. The patient exhibits a series of motor symptoms, such as static tremors, which impair their capacity to take care for themselves in daily life. In the late stage, the patient is unable to walk independently and is bedridden for an extended period of time, reducing their quality of life significantly. So far, treatment methods for PD mainly include drug therapy and deep brain stimulation. Pharmacotherapy is aimed at increasing dopamine (DA) levels; however, the treatment effect is more pronounced in the short term, and there is no benefit in improvement in the overall progression of the disease. In recent years, novel therapeutic strategies have been developed, such as cell reprogramming, trying to generate more DA in PD treatment. This review mainly discusses the advantages, methodology, cell origin, transformation efficiency, and practical application shortcomings of cell reprogramming therapy in PD strategy.