CNS & neurological disorders drug targets最新文献

Astrocytes are glial cells that perform several fundamental physiological functions within the brain. They can control neuronal activity and levels of ions and neurotransmitters, and release several factors that modulate the brain environment. Over the past few decades, our knowledge of astrocytes and their functions has rapidly evolved. Neurodegenerative diseases are characterized by selective degeneration of neurons, increased glial activation, and glial dysfunction. Given the significant role played by astrocytes, there is growing interest in their potential therapeutic role. However, defining their contribution to neurodegeneration is more complex than was previously thought. This review summarizes the main functions of astrocytes and their involvement in neurodegenerative diseases, highlighting their neurotoxic and neuroprotective ability.

Aim: We aimed to investigate the mechanisms involved in the neurotoxic effects of NDGA on differentiated and undifferentiated human neuroblastoma cells (MSN), assessing cell viability, changes in the actin cytoskeleton, cell migration and the expression of the 5-LOX enzyme and the inhibitor of cell cycle progression p21^WAF1/CIP1.

Background: High expression and activity of the lipoxygenase enzyme (LOX) have been detected in several tumors, including neuroblastoma samples, suggesting the use of LOX inhibitors as potential therapy molecules. Among these, the natural compound nordihydroguaiaretic acid (NDGA) has been extensively tested as an antiproliferative drug against diverse types of cancer cells.

Objective: In this study, we analyzed the toxic effect of NDGA on neuroblastoma cells at a dose that did not affect cell survival when they differentiated to a neuron-like phenotype and the potential mechanisms involved in the anticancer properties.

Methods: We exposed human neuroblastoma cells (MSN) to different concentrations of NDGA before and after a differentiation protocol with retinoic acid and nerve growth factor and analyzed cell viability, cell migration, actin cytoskeleton morphology and the levels of the cell cycle inhibitor p21^WAF1/CIP1 and 5-LOX.

Results: We found that differentiated human neuroblastoma cells are more resistant to NDGA than undifferentiated cells. The toxic effects of NDGA were accompanied by reduced cell migration, changes in actin cytoskeleton morphology, induction of p21^WAF1/CIP1 and decreased levels of the 5-LOX enzyme.

Conclusion: This study provides new evidence regarding the potential use of NDGA to induce cell death in human neuroblastoma.

Background: Alzheimer's disease is a neurodegenerative disorder characterized by severe cognitive, behavioral, and psychological symptoms, such as dementia, cognitive decline, apathy, and depression. There are no accurate methods to diagnose the disease or proper therapeutic interventions to treat AD. Therefore, there is a need for novel diagnostic methods and markers to identify AD efficiently before its onset. Recently, there has been a rise in the use of imaging techniques like Magnetic Resonance Imaging (MRI) and functional Magnetic Resonance Imaging (fMRI) as diagnostic approaches in detecting the structural and functional changes in the brain, which help in the early and accurate diagnosis of AD. In addition, these changes in the brain have been reported to be affected by variations in genes involved in different pathways involved in the pathophysiology of AD.

Methodology: A literature review was carried out to identify studies that reported the association of genetic variants with structural and functional changes in the brain in AD patients. Databases like PubMed, Google Scholar, and Web of Science were accessed to retrieve relevant studies. Keywords like 'fMRI', 'Alzheimer's', 'SNP', and 'imaging' were used, and the studies were screened using different inclusion and exclusion criteria.

Results: 15 studies that found an association of genetic variations with structural and functional changes in the brain were retrieved from the literature. Based on this, 33 genes were identified to play a role in the development of disease. These genes were mainly involved in neurogenesis, cell proliferation, neural differentiation, inflammation and apoptosis. Few genes like FAS, TOM40, APOE, TRIB3 and SIRT1 were found to have a high association with AD. In addition, other genes that could be potential candidates were also identified.

Conclusion: Imaging genetics is a powerful tool in diagnosing and predicting AD and has the potential to identify genetic biomarkers and endophenotypes associated with the development of the disorder.

Extracellular vesicles or exosomes, often known as EVs, have acquired significant attention in the investigations of traumatic brain injury (TBI) and have a distinct advantage in actively researching the fundamental mechanisms underlying various clinical symptoms and diagnosing the wide range of traumatic brain injury cases. The mesenchymal stem cells (MSCs) can produce and release exosomes, which offer therapeutic benefits. Exosomes are tiny membranous vesicles produced by various cellular entities originating from endosomes. Several studies have reported that administering MSC-derived exosomes through intravenous infusions improves neurological recovery and promotes neuroplasticity in rats with traumatic brain damage. The therapeutic advantages of exosomes can be attributed to the microRNAs (miRNAs), which are small non-coding regulatory RNAs that significantly impact the regulation of posttranscriptional genes. Exosome-based therapies, which do not involve cells, have lately gained interest as a potential breakthrough in enhancing neuroplasticity and accelerating neurological recovery for various brain injuries and neurodegenerative diseases. This article explores the benefits and drawbacks of exosome treatment for traumatic brain injury while emphasizing the latest advancements in this field with clinical significance.

Neurodegenerative conditions like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) encompass disorders characterized by the degeneration of neurons in specific circumstances. The quest for novel agents to influence these diseases, particularly AD, has unearthed various natural compounds displaying multifaceted activities and diverse pharmacological mechanisms. Given the ongoing extensive study of pathways associated with the accumulation of neurofibrillary aggregates and amyloid plaques, this paper aims to comprehensively review around 130 studies exploring natural products. These studies focus on inhibiting the formation of amyloid plaques and tau protein tangles, with the objective of potentially alleviating or delaying AD.

Neurodegenerative diseases represent a formidable global health challenge, affecting millions and imposing substantial burdens on healthcare systems worldwide. Conditions, like Alzheimer's, Parkinson's, and Huntington's diseases, among others, share common characteristics, such as neuronal loss, misfolded protein aggregation, and nervous system dysfunction. One of the major obstacles in treating these diseases is the presence of the blood-brain barrier, limiting the delivery of therapeutic agents to the central nervous system. Nanotechnology offers promising solutions to overcome these challenges. In Alzheimer's disease, NPs loaded with various compounds have shown remarkable promise in preventing amyloid-beta (Aβ) aggregation and reducing neurotoxicity. Parkinson's disease benefits from improved dopamine delivery and neuroprotection. Huntington's disease poses its own set of challenges, but nanotechnology continues to offer innovative solutions. The promising developments in nanoparticle-based interventions for neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), have offered new avenues for effective treatment. Nanotechnology represents a promising frontier in biomedical research, offering tailored solutions to the complex challenges posed by neurodegenerative diseases. While much progress has been made, ongoing research is essential to optimize nanomaterial designs, improve targeting, and ensure biocompatibility and safety. Nanomaterials possess unique properties that make them excellent candidates for targeted drug delivery and neuroprotection. They can effectively bypass the blood-brain barrier, opening doors to precise drug delivery strategies. This review explores the extensive research on nanoparticles (NPs) and nanocomposites in diagnosing and treating neurodegenerative disorders. These nanomaterials exhibit exceptional abilities to target neurodegenerative processes and halt disease progression.

Neurodegenerative disorders are characterized by a gradual but irreversible loss of neurological function. The ability to detect and treat these conditions successfully is crucial for ensuring the best possible quality of life for people who suffer from them. The development of effective new methods for managing and treating neurodegenerative illnesses has been made possible by recent developments in computer technology. In this overview, we take a look at the prospects for applying computational approaches, such as drug design, AI, ML, and DL, to the treatment of neurodegenerative diseases. To review the current state of the field, this article discusses the potential of computational methods for early disease detection, quantifying disease progression, and understanding the underlying biological mechanisms of neurodegenerative diseases, as well as the challenges associated with these approaches and potential future directions. Moreover, it delves into the creation of computational models for the individualization of care for neurodegenerative diseases. The article concludes with suggestions for future studies and clinical applications, highlighting the advantages and disadvantages of using computational techniques in the treatment of neurodegenerative diseases.

Diabetes is one of the major metabolic disorders of this era. It not only impacts a person's lifestyle but also has a long-term impact on the brain. It has a detrimental effect on a person's health when combined with hypertension and hyperlipidaemia. Several studies have suggested that the incidence of dementia is higher in people with metabolic syndrome. Investigations are underway to determine whether antidiabetic, hypolipidemic, hypercholesteraemic, anti-hypertensive, and other combination medicines can minimize the incidence of cognitive impairment. Some studies have suggested that anti-diabetic drugs like metformin, liraglutide, and dapagliflozin might enhance memory in long-term users. At the same time, other studies indicate that long-term insulin use may cause memory decline. Similarly, drugs like ACEIs, CCBs, fibrates, statins, and various nutraceuticals have been shown to improve cognition via multiple mechanisms. Literature suggests that drugs that can treat metabolic syndrome can also partially reduce the accumulation of beta-amyloid, whereas some studies contradict these findings. We review the past thirty years' of research work and summarize the effects of most commonly used drugs and nutraceuticals for treating metabolic syndrome on memory. Here, we review the effects of antidiabetic, hypolipidemic, anti-hypertensive, and hypercholesteremic, and their combination in learning and memory.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is normally linked to cognitive and functional dysfunctions. In this study, we explored the resting-state functional connectivity (rsFC) in the default mode network (DMN) to show the mechanism of neurophysiology in patients with OSAHS. Resting-state structural and functional Magnetic Resonance Imaging data were obtained from sixteen male moderate-to- severe patients with untreated OSAHS and 15 male matched healthy control subjects. The rsFC in the DMN was analyzed between OSAHS and healthy controls by the CONN software. Compared with the controls, the rsFC showed a significant decrease in the the medial prefrontal cortex, anterior cingulate and posterior cingulate, and showed an increase in the left inferior parietal lobule in OSAHS patients. The results indicated that the OSAHS patients presented alternatives of rsFC in the DMN compared with the controls.