CNS & neurological disorders drug targets最新文献

Inorganic fluoride is widely used in dental practices to treat problems like dental caries and prevent bone-related issues. Exposure to excess amounts of fluoride both through drinking water or other sources impairs vital functions of the body and can prove to be toxic, especially for the central nervous system. Sodium fluoride (NaF) crosses the blood-brain barrier in early developmental stages and causes impairments related to learning and memory, anxiety, decreased locomotor ability, and in some cases, depression-like behaviour, especially in children. Major mechanisms involved in this toxicity include reduction in levels of nicotinic and muscarinic receptors, autophagy, and apoptosis in neurons, decreased glucose consumption, inhibition of enzymes involved in the generation of energy and transmission of the synapse, mitochondrial dysfunction, and increased oxidative stress leading to inflammation and neuronal cell death. Out of all these, an increase in oxidative stress was reported to be one of the main mechanisms of fluoride-induced neurotoxicity. Based on these inferences, various natural compounds having antioxidant properties, like curcumin, aloe vera, quercetin, epigallocatechin gallate, etc. have been studied for their protective role in sodium fluoride-induced neurotoxicity. Involvement of other pathways like Nrf2/Keap pathways, SIRT3, etc., have warranted a need for further detailed study to identify other potential therapeutic targets like AMPK to prevent/treat fluoride-induced neurotoxicity. The present review captures fluoride, its role in neurodevelopment, and mechanisms & pathways involved by which fluoride can hurt neurodevelopment & how AMPK can be a possible therapeutic target.

Chemotherapy-induced pain is one of the major challenges that hamper the patient's quality of life. Several cases of insufficient pain management were reported globally, especially in the case of patients who do not respond well to conventional pain management regimes and opioid analgesics. Additionally, conventional pain management has several shortcomings, and evidence suggests that cannabidiol has the potential to overcome those shortcomings. Cannabidiol (CBD) is a non-psychoactive compound of the Cannabis plant that shows an effective outcome in chemotherapy- induced pain as well as in cancer treatment, as it possesses anti-inflammatory and analgesic properties. The mechanism of pain and its management by cannabidiol, with all possible evidence, is well summarised in the paper. This article concludes the types of pain experienced by cancer patients, the effectiveness of CBD in the management of pain, and challenges faced by patients after using Cannabidiol with various case studies. Later, antitumor efficacy studies of CBD were disclosed, and its various types of formulations and nano-formulations were summarized in the paper. Overall, the paper establishes the role of cannabidiol in Chemotherapy-induced pain.

Opioid addiction is a condition of the central nervous system that occurs as a result of using opiate-based substances, which can be either natural or synthetic chemicals. These have effects identical to those of morphine and work by interacting with opioid receptors such as morphine, heroin, opium, buprenorphine, and Oxycontin. Dopamine has been suggested to play a role in the mechanisms linked to opioid addiction. Additionally, neurotransmitters such as serotonin, norepinephrine, glutamate, and GABA may also have a significant impact. These processes play a critical role in the formation of brain circuits that are involved in the development of addictive behavior. The PI3K-Akt-mTOR pathway is widely recognized as an essential regulator of the effects induced by neurotransmitters on synaptic plasticity, protein synthesis, and cellular responses. This interplay has considerable importance in the development and persistence of opioid addiction, impacting several domains, including reward processing, stress reactivity, and brain plasticity. The understanding of these neurochemical modifications provides vital insights into the underlying mechanisms of addiction and presents potential pathways for treatments. The review enlisted the clinical trials of different types of opioid addiction or dependence. The review offers a succinct summary of many studies that establish a correlation between the PI3K/Akt-mTOR signaling pathway and various receptors implicated in multiple forms of opioid-related dependency.

A family of peptides known as bioactive peptides has unique physiological properties and may be used to improve human health and prevent illness. Because bioactive peptides impact the immunological, endocrine, neurological, and cardiovascular systems, they have drawn a lot of interest from researchers. According to recent studies, bioactive peptides have a lot to offer in the treatment of inflammation, neuronal regeneration, localized ischemia, and the blood-brain barrier. It investigates various peptide moieties, including antioxidative properties, immune response modulation, and increased blood-brain barrier permeability. It also looks at how well they work as therapeutic candidates and finds promising peptide-based strategies for better outcomes. Furthermore, it underscores the need for further studies to support their clinical utility and suggests that results from such investigations will enhance our understanding of the pathophysiology of these conditions. In order to understand recent advances in BPs and to plan future research, academic researchers and industrial partners will find this review article to be a helpful resource.

Although electroconvulsive therapy (ECT) has immediate and profound effects on severe psychiatric disorders compared to pharmacotherapy, the mechanisms underlying its therapeutic effects remain elusive. Increasing evidence indicates that glial activation is a common pathogenetic factor in both major depression and schizophrenia, raising the question of whether ECT can inhibit glial activation. This article summarizes the findings from both clinical and experimental studies addressing this key question. Based on the findings, it is proposed that the suppression of glial activation associated with neuroinflammation may be involved in the mechanism by which ECT restores brain homeostasis and exerts its therapeutic effects.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with a complex, multiple etiology that is marked by impaired social interaction, communication, and repetitive behaviour. There is presently no pharmaceutical treatment for the core symptoms of ASD, even though the prevalence of ASD is increasing worldwide. Treatment of autism spectrum disorder involves the interaction of numerous signalling pathways, such as the Wnt/beta-catenin pathway, probiotics and kynurenine pathway, PPAR pathway, PI3K-AKT-mTOR pathway, Hedgehog signaling pathway, etc. The scientific literature has revealed TWEAK/Fn14 to not be explored in the autism spectrum disorder. In vitro and in vivo, TWEAK can control a wide range of cellular responses. Recent research has revealed that TWEAK and Fn14 are expressed in the Central Nervous System (CNS) and upregulated in perivascular endothelial cells, astrocytes, neurons, and microglia in response to various stimuli, including cerebral ischemia. This upregulation is followed by cell death and an increase in Blood-brain Barrier (BBB) permeability. The study has revealed that Aurintricarboxylic Acid (ATA) acts as an agent that suppresses TWEAK/Fn14 signaling. Similarly, from the discussion, it has been emphasized that the proposed molecular TWEAK/Fn14 signalling pathway can be considered as a therapeutic approach in the management of autism spectrum disorder.

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.

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.

Sodium channels are necessary for electrical activity in modules of the nervous system. When such channels fail to work properly, it may cause different neurological diseases. This review will discuss how particular mutation in these channels leads to different diseases. Positive alterations can lead to such diseases as epilepsy, or any muscle disorder due to over activation of neurons. Conversely, loss-of-function mutations may cause heart diseases and problems regarding motor and mental activity since neurons are not functioning well because of lost machinery. The review would discuss over familiar channelopathies such as genetic epilepsies, the familial hemiplegic migraine, and Para myotonia congenital and relatively new interrelations with the complex ailments including Alzheimer's, Parkinson's and multiple sclerosis. Thus, knowledge of these mechanisms is important in designing specific therapeutic approaches. There is a rationale for altering the sodium channel activity in the treatment of these neurological disorders by drugs or indeed genetic methods. Thus, the review is undertaken to provide clear distinctions and discuss the issues related to sodium channel mutations for the potential development of individualized medicine. The review also gives information on the function and general distribution of voltage-gated sodium channels (VGSCs), how their activity is controlled, and what their structure is like. The purpose therefore is to draw understanding over the apparently multifaceted functions exerted by VGSCs in the nervous system relative to several diseases. This knowledge is imperative in the attempt to produce treatments for these disabling disorders.

Dr. Aloysius Alzheimer, a German neuropathologist and psychiatrist, recognized the primary instance of Alzheimer's disease (AD) for a millennium, and this ailment, along with its related dementias, remains a severe overall community issue related to health. Nearly fifty million individuals worldwide suffer from dementia, with Alzheimer's illness contributing to between 60 and 70% of the instances, estimated through the World Health Organization. In addition, 82 million individuals are anticipated to be affected by the global dementia epidemic by 2030 and 152 million by 2050. Furthermore, age, environmental circumstances, and inherited variables all increase the likelihood of acquiring neurodegenerative illnesses. Most recent pharmacological treatments are found in original hypotheses of disease, which include cholinergic (drugs that show affective cholinergic system availability) as well as amyloid-accumulation (a single drug is an antagonist receptor of Nmethyl D-aspartate). In 2020, the FDA provided approval on anti-amyloid drugs. According to mounting scientific data, this gut microbiota affects healthy physiological homeostasis and has a role in the etiology of conditions that range between obesity and neurodegenerative disorders like Alzheimer's. The microbiota-gut-brain axis might facilitate interconnection among gut microbes as well as the central nervous system (CNS). Interaction among the microbiota-gut system as well as the brain occurs through the "two-way" microbiota-gut-brain axis. Along this axis, the stomach as well as the brain develop physiologically and take on their final forms. This contact is constant and is mediated by numerous microbiota-derived products. The gut microbiota, for instance, can act as non-genetic markers to set a threshold for maintaining homeostasis or getting ill. The scientific community has conducted research and found that bowel dysbiosis and gastrointestinal tract dysregulation frequently occur in Alzheimer's disease (AD) patients. In this review, the effects of the microbiota- gut-brain axis on AD pathogenesis will be discussed.