Degenerative neurological and neuromuscular disease最新文献

Objective: To report the clinical and genetic characteristics of a rare Charcot-Marie-Tooth disease type 2F (CMT2F) pedigree, and to explore the phenotypic diversity and diagnostic essentials of the mutation in combination with literature review.

Methods: The clinical data, electrophysiological findings, and genetic testing results of the proband and pedigree members were retrospectively analyzed, and relevant literatures were reviewed for comparative analysis.

Results: Both patients had an onset in middle and old age (50/66 years), presenting with distal lower limb muscle weakness (Grade III), muscle atrophy, absent tendon reflexes, pes cavus, and sensory abnormalities. Serum creatine kinase (CK) was elevated (474 U/L), and electromyography indicated axonal peripheral nerve damage. Genetic testing revealed a heterozygous mutation of HSPB1 gene c.418C>G [p.Arg140Gly], which was verified by co-segregation in the pedigree. Literature review showed that this mutation causes axonal transport dysfunction by impairing the chaperone function of HSP27.

Conclusion: This study expands the phenotypic spectrum of late-onset CMT2F, with some patients showing mild elevation of serum CK. It provides new clinical evidence for the pathogenicity of this mutation.

Purpose: The symptoms of patients with early to mid-stage Parkinson's disease (PD) are closely associated with their quality of life. However, few studies have explored the relationship between symptoms and quality of life. This study aims to investigate the symptom profiles of patients with early to mid-stage PD, construct a symptom network to identify core symptoms, and examine their associations with quality of life.

Patients and methods: This cross-sectional study was conducted from November 2024 to February 2025 among 954 patients with early to mid-stage PD in China, with stages 1-2 classified as early stage and stage 3 as mid stage. All participants completed the PD Symptom Experience Scale. Network models were constructed using R version 4.4.3 to identify core symptoms, describe inter-symptom relationships, and calculate centrality indices.

Results: The top three symptoms in terms of prevalence were bradykinesia (77.46%), resting tremor (75.05%), and rigidity (59.01%). The most severe symptom was resting tremor. In the symptom network analysis, the top three symptoms with the highest node centrality were bradykinesia (r_e=1.27), postural instability (r_e=1.16), and limb stiffness (r_e=1.96). In the quality of life network, the dimensions with the highest node centrality were "mobility" (r_be=0.52), "emotional well-being" (r_be=0.50), and "cognitions" (r_be=0.49). "Mobility" was positively correlated with difficulty turning over in bed (r=0.19), freezing of gait (r=0.09), and difficulty standing up or sitting down (r=0.08).

Conclusion: Multiple symptoms were simultaneously experienced by patients with early to mid-stage PD, and interrelationships among symptoms were observed. Bradykinesia was identified as the core symptom, and the "mobility" dimension was recognized as the central node in the quality of life network. Healthcare providers are advised to comprehensively consider patients' overall symptom profiles and their relationships with quality of life, and to implement targeted, integrated interventions.

Introduction: Amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA) are both neurodegenerative disorders. While ALS may present with clinical features resembling Parkinsonism, there have been no definitive reports of ALS mimicking MSA, only cases of Primary lateral sclerosis (PLS) mimicking Parkinsonism.

Methods: This article reports a case of ALS presenting with Parkinsonism and anxiety as the initial symptoms. Five years after the initial diagnosis of MSA, the patient developed signs of lower motor neuron involvement, including fasciculations and muscle atrophy, ultimately leading to a revised diagnosis of ALS. This study combines literature analysis to explore the reasons for misdiagnosis and identifies key differentiating features.

Results: Specifically, muscle rigidity in ALS is characterized by a velocity-dependent increase in muscle tone caused by damage to the upper motor neurons. This symptom tends to be more pronounced in the lower limbs than in the upper limbs and is often accompanied by spastic gait. Objective examinations may reveal early atrophy of the frontal and temporal lobes of the cerebrum on head magnetic resonance (MR) imaging, whereas ¹⁸F-FDG brain positron emission tomography (PET) may reveal reduced metabolism in the frontal and parietal lobes of the cerebrum with normal basal ganglial function, distinguishing ALS from basal ganglial metabolic decline in MSA.

Discussion: To our knowledge, this is the first case of ALS misdiagnosed as MSA. Clinically, patients with parkinsonism who do not respond to dopaminergic drugs should be cautious about atypical ALS. Muscle rigidity manifesting as upper motor neuron damage, and MR and ¹⁸F-FDG brain PET imaging can provide early differential diagnosis indicators.

Background: The aim was to investigate the potential role of TP73-AS1 in the pathogenesis of Parkinson's disease.

Methods: Peripheral blood samples were obtained from three patients with early-onset Parkinson's disease (PD), three patients with late-onset PD, and three healthy controls for the extraction of total RNA. Genomic long non-coding RNA (lncRNA) expression levels were analyzed using the Illumina HiSeq2500 sequencing platform. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to study the expression of TP73-AS1. Flow cytometry and Western blot analyses were conducted to assess the functional role of TP73-AS1 in SH-SY5Y cells in vitro. Moreover, the expression of inflammatory cytokines, such as IL-16, IL-6, and α-synuclein (SYN), was examined using cellular immunofluorescence techniques.

Results: Among early-onset PD patients, 59 lncRNAs were significantly upregulated, and 57 lncRNAs were significantly downregulated compared to the control group. Similarly, late-onset PD patients showed 70 upregulated lncRNAs and 77 downregulated lncRNAs with statistical significance compared to the control group. In vitro studies indicated a significant increase in lncRNA TP73-AS1 expression in the MPP+-treated group in contrast with the control group (P < 0.001). Furthermore, the MPP+-treated group displayed elevated levels of Cleaved caspase-3, IL-16, as well as IL-6 (P < 0.001). Conversely, Bcl-2 expression decreased, Bax expression increased, and the Bax/Bcl-2 expression ratio demonstrated an increase (P < 0.001). Reducing lncRNA TP73-AS1 resulted in decreased apoptosis and inflammation, along with a decrease in α-SYN expression (P < 0.001). Notably, the absence of TP73-AS1 showed a protective effect against PD, suggesting it to be a potential target for the treatment of PD. These findings suggest that TP73-AS1 may serve as a potential molecular marker for the early diagnosis of PD, providing a new perspective for understanding the regulatory mechanisms of inflammation and apoptosis in PD.

Parkinson's disease is a neurodegenerative disorder that leads to neuronal loss. Though a variety of genetic and environmental factors may be involved in the etiology, the presentation of the disorder is very similar. Trace minerals such as manganese are essential for brain development and function though effective concentrations are paramount. Exposure to high concentrations of manganese is known to cause neurotoxicity and has been recently associated with manganese-induced parkinsonism, which will be explored in this review. This review synthesizes findings from peer-reviewed clinical, epidemiological, and experimental studies to explore the underlying mechanisms and contributing factors of manganese-induced parkinsonism. Specifically, it examines alterations in lipidomic and oxidative profiles, enhancement of redox cycling, transporter dysfunction and deficiency, ion homeostasis, dysregulation of signaling pathways and autophagy, mRNA disruption, dopamine toxicity, manganese contamination, and neuroprotective mechanisms. Preventative and therapeutic interventions-including chelation therapy with ethylene-diamine-tetra-acetic acid (CaNa₂EDTA), with or without plasma exchange and para-aminosalicylic acid (PAS), as well as natural compounds such as vinpocetine (VIN), punicalagin (PUN), niacin, vitamin E, DNLA, curcumin, and sesame oil-are also reviewed. Given manganese's role as an oxidant in the synthesis of neurotoxic compounds, therapeutic strategies targeting both manganese, its associated molecular pathways, and its downstream neurotoxic effects may represent the most promising direction for future research.

Background: Apoptosis and immune inflammation play important roles in the pathological process of Alzheimer's disease (AD), but their specific pathogenesis is still unclear. Therefore, this article focuses on exploring the effects of Danzhi Xiaoyao Powder (DXP) on the learning and memory ability of AD model rats from the dual mechanisms of apoptosis and immune inflammation.

Methods: The AD model was replicated by injecting Okadaic acid (100 ng) into the bilateral hippocampus of rats. Successful rats were selected and orally administered with donepezil hydrochloride and DXP decoction for 42 days. Their learning and memory abilities, hippocampal morphology, Aβ expression, inflammatory factors, apoptotic factors, anti apoptotic factors, as well as the expression of pathway proteins and mRNA were detected.

Results: After DXP intervention, the learning and memory abilities of rats improved, the neuronal cell arrangement was more complete, the expression of Aβ decreased, the expression of pro-inflammatory cytokine and apoptotic factors decreased, the expression of anti apoptotic factors increased, Protein Kinase B (Akt) expression and activity significant up-regulation, and nuclear factor kappa-B (NF-κB), p38 MAPK (p38), MAPKAPK-2 (MK2), Cyclooxygenase-2 (COX-2) protein and mRNA expression were significantly down-regulated.

Conclusion: DXP can improve the learning and cognitive abilities of AD model rats, and its mechanism of action may be related to the regulation of the Akt/NF-κB apoptosis pathway mediated by NF-κB interaction and the p38MAPK/MK2/COX-2 immune inflammatory dual pathway.

The CRISPR system has emerged as a ground-breaking gene-editing tool, offering promising therapeutic potential for Duchenne muscular dystrophy (DMD), a severe genetic disorder affecting approximately 1 in 5000 male births globally. DMD is caused by mutations in the dystrophin gene, which encodes a critical membrane-associated protein essential for maintaining muscle structure, function and repair. Patients with DMD experience progressive muscle degeneration, loss of ambulation, respiratory insufficiency, and cardiac failure, with most succumbing to the disease by their third decade of life. Despite the well-characterized genetic basis of DMD, curative treatments- such as exon skipping therapies, micro-dystrophin, and steroids- remain elusive. Recent preclinical studies have demonstrated the promise of CRISPR-based approaches in restoring dystrophin expression across various models, including human cells, murine systems, and large animal models. These advancements highlight the potential of gene editing to fundamentally alter the trajectory of the disease. However, significant challenges persist, including immunogenicity, off-target effects, and limited editing efficiency, which hinder clinical translation. This review provides a comprehensive analysis of the latest developments in CRISPR-based therapeutic strategies for DMD. It emphasizes the need for further innovation in gene-editing technologies, delivery systems, and rigorous safety evaluations to overcome current barriers and harness the full potential of CRISPR/Cas as a durable and effective treatment for DMD.

Duchenne Muscular Dystrophy (DMD) is an inherited, X-linked disorder that is progressive, debilitating, and ultimately fatal. The current therapeutic landscape offers no cures, but does include palliative treatments that delay disease progression, and there is progress on genetic therapies that have the promise to be curative. There is much room for new therapies, and foundational work with the estrogen receptor modulator tamoxifen suggests the potential of a unique spectrum of therapeutic benefit from endoxifen, a metabolite of tamoxifen. Here we describe the potential for this new DMD therapy in the context of the overall DMD therapeutic landscape.

Background: Cold inducible RNA-binding protein (CIRP) is an important danger-associated molecular pattern involved in tissue-specific and systemic inflammation related to inflammation and Alzheimer's disease (AD). However, the precise roles and mechanism of CIRP in the functional changes in astrocytes during the development of AD are still unknown. This study aimed to assess gene expression alterations in astrocytes after they overexpress CIRP (oe-CIRP) and to explore the relationship between abnormal CIRP expression and AD.

Methods: We created astrocyte cell lines with a CIRP or control vector expression using three human glioma cell lines U87, U251 and H4, and analyzed the mRNA expression profiles of 3 pairs of cells via microarray. Bioinformatics identified differentially expressed mRNAs between CIRP-overexpressing (ov-CIRP) and control groups, validated by q-PCR and Western blotting (WB). Finally, the effect of CIRP overexpression in astrocytes on neurons was observed in a coculture system.

Results: We identified 119 mRNAs with obvious fold changes between the ov-CIRP and control groups for all 3 pairs of human glioma cell lines. The biological functional analysis indicated that urokinase plasminogen activator (uPA), a gene whose expression significantly decreased after CIRP overexpression, was closely associated with AD. WB and q-PCR confirmed that CIRP overexpression significantly inhibited uPA at both mRNA and protein levels in U87, U251 and H4 cells. Moreover, compared with those cocultured with control astrocytes, SH-SY5Y cells cocultured with CIRP-overexpressing astrocytes exhibited a significant increase in the expression of amyloid-β (Aβ)1-42 and the hyperphosphorylated microtubule-associated protein tau (Tau).

Conclusion: CIRP overexpression in astrocytes inhibits uPA expression, promoting Aβ1-42 production and tau phosphorylation in neurons, thereby increasing AD risk. These results suggest that the overexpression of CIRP in astrocytes contributes to the development of AD.

Purpose: Multiple sclerosis (MS) is a neurological disorder affecting almost 2.8 million people globally, approximately 80-85% of whom have the relapsing-remitting form of the disease (RRMS). There are several autoinjectors available for the administration of injectable disease-modifying therapies for the treatment of MS. The objective of the current study was to gain an understanding of factors related to patients' and nurses' autoinjector preferences, and to evaluate two autoinjectors for glatiramer acetate (MyJECT™ and CSYNC™) against those preferences.

Patients and methods: Patients with RRMS and nurses experienced in training patients with an autoinjector were recruited from 12 health centers in Germany. Surveys were administered to patients and nurses and their answers to 13 questions over five categories (participants' characteristics, important autoinjector attributes, autoinjector performance, satisfaction with the autoinjector devices and demographics) were scored, where appropriate, using a 5-point Likert scale.

Results: A total of 15 patients and 15 nurses were included in the study. Overall, the top four most important attributes, for both nurses and patients, were ease of handling, ability to use independently, ease of gripping the autoinjector and ease of self-injection. MyJECT™ received a mean score of at least 4.5 (out of 5) on more attributes than CSYNC™ and satisfaction with both autoinjectors was high.

Conclusion: Nurses and patients with RRMS were highly satisfied with both the MyJECT™ and CSYNC™ autoinjectors, with scores suggesting that MyJECT™ performs better on the attributes they identified as most important. All patients currently using the MyJECT™ were likely or highly likely to recommend it to another patient with RRMS.