CNS & neurological disorders drug targets最新文献

Promoting neuroplasticity for better recovery and function restoration has lately become the focus of rehabilitation techniques for individuals with neurologic disorders. A rapidly expanding medical specialty, neuromodulation includes a broad variety of methods for activating particular neurological pathways, such as Transcranial magnetic stimulation (TMS), Transcranial direct current stimulation (tDCS), peripheral nerve stimulation, and SCS, among many others. Research on the use of neuromodulation in the context of spinal cord injury (SCI) is limited, in contrast to the abundance of literature on its potential benefits in chronic pain treatment. Combining exercise with non-invasive neuromodulation improves recovery outcomes for some patient groups, according to our research. While we mostly focus on the motor components of recovery, we do briefly mention the non-motor effects of these disorders. The difficulties of applying ideas in clinical practice and the gaps in the existing research are also brought to light. In order to better customize the individual neuroplastic responses associated with each disease, we identify research gaps and propose routes for future investigations. This review is useful for rehabilitation professionals and researchers since it focuses on neuroplastic exercise treatments for specific illnesses and diagnoses. Few studies have used long-term randomized-controlled trials, even though these approaches have great promise for enhancing overall functionality and impairment levels. If these novel modalities may be therapeutically employed to reduce pain, restore function, and improve the quality of life for individuals impacted, then more study is required to support them.

Background: Memory loss and cognitive decline are prominent symptoms of various neurodegenerative diseases, impacting daily activities and posing a significant burden on healthcare systems. The study aimed to explore the effect of barbigerone against LPS-induced memory impairment in rats and may offer novel therapeutics for neurodegenerative diseases.

Methods: A total of 30 male Wistar rats were utilized and subsequently divided into five distinct experimental groups: group I received saline water as a control, group II- received LPS, group III - received LPS, and barbigerone (10 mg/kg/p.o.), group IV- received LPS and a higher dose of barbigerone (20 mg/kg/p.o.), and group V -barbigerone alone (20 mg/kg/p.o.). Behavioural test was performed through the Morris water maze and Y-maze test. Biochemical markers such as oxidative, proinflammatory, apoptotic, and further molecular docking and simulations elucidate the mechanisms of barbigerone effects.

Results: Barbigerone significantly improved the learning capacity of rats in both the MWM and Ymaze tests, indicating enhanced memory and reduced latency times. Furthermore, barbigerone exhibited beneficial effects on oxidative stress and inflammation markers, suggesting its potential to protect against neuronal damage and promote cognitive function. Based on molecular docking, barbigerone showed a greater binding affinity with different intermolecular interactions; among them, NF-KB (ISVC) had the most potent interaction. Molecular dynamics simulations were performed to assess the stability and convergence of complexes formed by Barbigerone with 1NME_ Barbigerone, 1SVC_Barbigerone, and 4AQ3 4AQ3_Barbigerone.

Conclusion: These findings demonstrate that barbigerone possesses neuronal protective effects against LPS-induced memory deficits in rats by restoring endogenous antioxidant and pro-inflammatory cytokines.

Background: A major issue with neurodegenerative diseases is cholinergic depletion, the development of oxidative stress, and the reduction in the ability to control the expression of genes involved in the regulation of neurogenesis. The most widespread neurodegenerative disease is Alzheimer's disease (AD). Current treatments are not able to improve the symptoms of the disease. Thus, selecting or creating a safe and effective drug is very important.

Objective: In this context, the potential of sweroside (Swe) to regulate acetylcholinesterase (AChE) activity, malondialdehyde (MDA) level, and bdnf, npy, egr1, nfr2a, and creb1 gene expression in the scopolamine (Sco)-induced zebrafish model of cognitive impairment was investigated.

Methods: Swe was administered daily for 16 days chronically to zebrafish at concentrations of 1 μg/L, 3 μg/L, and 5 μg/L whereas Sco (100 μM) was given to zebrafish for 30 min.

Results: Exposure to Swe decreased AChE activity and MDA level along with upregulating of gene expression in the brain of the Sco-induced zebrafish model.

Conclusion: Overall, our findings suggested that Swe has a positive role in the cholinergic system activity and brain antioxidant status and showed for the first time that it can restore the downregulated expression of bdnf, npy, egr1, nfr2a, and creb1 genes in the brain of the Sco-induced zebrafish model.

Neurological conditions resulting from severe spinal cord injuries, brain injuries, and other traumatic incidents often lead to the loss of essential bodily functions, including sensory and motor capabilities. Traditional prosthetic devices, though standard, have limitations in delivering the required dexterity and functionality. The advent of neuroprosthetics marks a paradigm shift, aiming to bridge the gap between prosthetic devices and the human nervous system. This review paper explores the evolution of neuroprosthetics, categorizing devices into sensory and motor neuroprosthetics and emphasizing their significance in addressing specific challenges. The discussion section delves into long-term challenges in clinical practice, encompassing device durability, ethical considerations, and issues of accessibility and affordability. Furthermore, the paper proposes potential solutions with a specific focus on enhancing sensory experiences and the importance of user-friendly interfaces. In conclusion, this paper offers a comprehensive overview of the current state of neuroprosthetics, outlining future research and development directions to guide advancements in the field.

There is a myriad of activities that involve mitochondria that are crucial for maintaining cellular equilibrium and genetic stability. In the pathophysiology of neurodegenerative illnesses, mitochondrial transcription influences mitochondrial equilibrium, which in turn affects their biogenesis and integrity. Among the crucial proteins for keeping the genome in optimal repair is mitochondrial transcription factor A, more commonly termed TFAM. TFAM's non-specific DNA binding activity demonstrates its involvement in the control of mitochondrial DNA (mtDNA) transcription. The role of TFAM in controlling packing, stability, and replication when assessing the quantity of the mitochondrial genome is well recognised. Despite mounting evidence linking lower mtDNA copy numbers to various age-related diseases, the correlation between TFAM abundance and neurodegenerative disease remains insufficient. This review delves into the link between neurodegeneration and mitochondrial dysfunction caused by oxidative stress. Additionally, the article will go into detail about how TFAM controls mitochondrial transcription, which is responsible for encoding key components of the oxidative phosphorylation (OXPHOS) system.

Parkinson's disease (PD) is a progressive neurological condition characterized by both dopaminergic and non-dopaminergic brain cell loss. Patients with Parkinson's disease have tremors as a result of both motor and non-motor symptoms developing. Idiopathic Parkinson's disease (idiopathic PD) prevalence is increasing in people over 60. The medication L-dopa, which is now on the market, merely relieves symptoms and has several negative effects. In this article, we highlight the therapeutic potential of glucagon-like peptide-1, adenosine A2A, and cannabinoid receptors as attractive targets for enhancing neuroprotection and reducing a variety of motor and non-motor symptoms. Recent research has widened knowledge of new therapeutic targets and detailed cellular mechanisms, providing invaluable insights into the essential roles of cannabinoid receptors, adenosine A2A receptors, and glucagon-like peptide-1 receptors in PD pathogenesis and unique opportunities for drug development for mankind globally.

Background: Botulinum Toxin type A (BonTA) is the preferred treatment for Cervical Dystonia (CD). However, the success rate is often suboptimal. One of the reasons for treatment failure is the in accuracy of injections. Some physicians rely on Anatomical Landmarks (AL) for injections, while others use either Ultrasound (US) or Electromyography guidance (EMGg) to improve accuracy.

Methods: This retrospective two-center study compared the therapeutic outcomes of AL-based and EMGg injections with USg injections. Demographic and clinical assessments of previous visits and current visits were recorded between 2019 and 2023.

Results: Fifty-one patients were included. Six patients were injected using AL, 14 patients under EMGg, and 31 patients received USg injections. Pain relief was significantly lower for the AL group (40.0% ± 22.4%) compared to both USg and EMGg (81.2% ± 34.0% and 82.2% ± 10.3%, respectively; p = 0.001). Dysphagia was reported in 7.1% of EMGg and 16% of the USg group and none of those treated with AL (p > 0.05).

Conclusion: The results of this study demonstrated that the clinical outcomes of USg and EMGg BonTA injections are comparable and both techniques are superior to AL. The main side effect observed was dysphagia, which was more common in the USg group, although without reaching statistical significance.

Background: AD is a demyelinating disease. Myelin damage initiates the pathological process of AD, resulting in abnormal synaptic function and cognitive decline. The myelin sheath formed by oligodendrocytes (OL) is a crucial component of white matter. Investigating AD from the perspective of OL may offer novel diagnostic and therapeutic perspectives.

Objectives: This study aimed to analyze the association between OL-related genes and Alzheimer's disease (AD) using bioinformatics and verify this association via molecular biology experiments.

Methods: The AD datasets were acquired from the Gene Expression Omnibus (GEO) database of NCBI. Consensus clustering was employed to determine the subtypes of AD, followed by evaluating the clinical characteristics of these subtypes. Subsequently, immune infiltration analysis of relevant genes and Weighted Gene Co-expression Network Analysis (WGCNA) were conducted to identify modules and hub genes associated with AD progression. The intersection of genes obtained was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. To narrow down the scope and identify OL-related genes with diagnostic potential, three machine learning algorithms were utilized. In addition, the eXtreme Sum (XSum) algorithm was used to screen small molecule drug candidates based on the connectivity map (CMAP) database. Finally, these identified genes were validated using Real-time fluorescence quantitative PCR (RT-qPCR).

Results: Among the three subtypes of AD, Cluster A and Cluster C exhibited increased levels of Braak and neurofibrillary tangles compared to Cluster B. The proportion of females was greater than that of males among the three subclasses of AD. There were no significant differences in age among the three subclasses, but significant differences in gene expression existed. Through WGCNA analysis, 108 genes were identified. Among these, 16 genes were identified as shared genes by the least absolute shrinkage and selection operator (LASSO), random forest (RF), and support vector machines (SVM) algorithms, and logistic regression further determined 11 genes. The establishment of a nomogram demonstrated the significance of these 11 genes in AD. The "XSum" algorithm revealed five drugs with therapeutic potential for AD. qPCR analysis revealed the upregulation and downregulation of the highlighted genes. According to this study, 11 genes related to OL were also found to be associated with immune cell infiltration in AD patients. These genes demonstrated potential diagnostic value for AD. Additionally, we screened five small molecular drugs that exhibit potential therapeutic effects on AD.

Conclusion: This research provides a new perspective for personalized clinical management and treatment of AD.

Parkinson's disease (PD) is a neurodegenerative disorder that results from the progressive loss of neurons in the brain followed by symptoms such as slowness and rigidity in movement, sleep disorders, dementia and many more. The different mechanisms due to which the neuronal degeneration occurs have been discussed, such as mutation in PD related genes, formation of Lewy bodies, oxidation of dopamine. This review discusses current surgical treatment and gene therapies with novel developments proposed for PD. Gene therapy based on novel approaches will possess more potential advantages over the conventional methods. Currently, gene therapy for such disorders is still under the process of clinical trials and approval. The pathogenesis comes from the breakdown of dopaminergic neurons within substantia nigra (SN) by the action of tyrosinase enzyme and subsequent accumulation of α-synuclein within the neurons. These dopaminergic neurons are the main source of dopamine, the decline of which is responsible for the symptoms. So, gene therapy can possibly provide more stable supplementation and regulate the expression of tyrosinase enzyme, providing better symptomatic relief and lesser side effects. Dopamine replacement therapy is a wellstudied gene therapy method for PD. Another approach involves introducing functional genes for enzymes such as tyrosine hydroxylase, cyclohydrolases, and decarboxylases with the help of engineered vectors such as AAV and LV. Further, the potential application of nanoparticles in gene therapy as an efficient gene delivery and imaging system has been discussed. Among these, lipidbased nanoparticles such as PILs offer important benefits in terms of enhanced bioavailability, permeability to the cells, and solubility. So, this review paper summarizes some of the advanced gene therapy approaches for PD and the current status of clinical research in the development of gene therapy using nanoparticles.

Neurodisease, caused by undesired substances, can lead to mental health conditions like depression, anxiety and neurocognitive problems like dementia. These substances can be referred to as contaminants that can cause damage, corruption, and infection or reduce brain functionality. Contaminants, whether conceptual or physical, have the ability to disrupt many processes. These observations motivate us to investigate contaminants and neurotoxicity collaboratively. This study investigates the link between pollutants and neuro-disease, examining transmission pathways and categorization. It also provides information on resources, causes, and challenges to minimize contamination risks. Contamination may cause various neuro-diseases, including Alzheimer's, Parkinson's, multi-system atrophy, Huntington's, autism spectrum disorder, psychiatric disorder, dementia, meningitis, encephalitis, schizophrenia, anxiety, and depression. The negative effects depend on the nature and extent of exposure. A comprehensive literature search was conducted using databases such as PubMed and Scopus, focusing on studies published till 2024. Studies were selected based on their examination of the relationship between environmental contaminants and brain health, emphasizing transmission pathways and the resulting neurological outcomes. Findings indicate that contaminants can penetrate the blood-brain barrier (BBB) via nasal, gut, and auditory routes, triggering harmful neurophysiological processes. This review highlights the urgent need for increased global awareness, policy interventions, and preventive measures to mitigate the long-term impacts of environmental contaminants on brain health, particularly in emerging nations.