Pentylenetetrazole (PTZ)-induced seizure is one of the gold standard mouse models for rapid evaluation of novel anticonvulsants. Synchronically, PTZ induced kindling in mice is also a simple and well ...accepted model of chronic epilepsy. PTZ kindling has been explored for studying epileptogenesis, epilepsy-associated comorbidities, and refractory epilepsy. This review summarizes the potential of PTZ kindling in mice and its modifications for its face, construct, and predictive validity to screen antiepileptogenic drugs, combined or add on novel and safe therapies for treatment of epilepsy-associated depression and cognitive impairment as well as effective interventions for pharmacoresistant epilepsy.
Neuroinflammation is one of the host defensive mechanisms through which the nervous system protects itself from pathogenic and or infectious insults. Moreover, neuroinflammation occurs as one of the ...most common pathological outcomes in various neurological disorders, makes it the promising target. The present review focuses on elaborating the recent advancement in understanding molecular mechanisms of neuroinflammation and its role in the etiopathogenesis of various neurological disorders, especially Alzheimer’s disease (AD), Parkinson’s disease (PD), and Epilepsy. Furthermore, the current status of anti-inflammatory agents in neurological diseases has been summarized in light of different preclinical and clinical studies. Finally, possible limitations and future directions for the effective use of anti-inflammatory agents in neurological disorders have been discussed.
Flavonoids, a group of natural dietary polyphenols, are known for their beneficial effects on human health. By virtue of their various pharmacological effects, like anti-oxidative, antiinflammatory, ...anti-carcinogenic and neuroprotective effects, flavonoids have now become an important component of herbal supplements, pharmaceuticals, medicinals and cosmetics. There has been enormous literature supporting neuroprotective effect of flavonoids. Recently their efficacy in various neurodegenerative diseases, like Alzheimer's disease and Parkinson diseases, has received particular attention.
The mechanism of flavanoids neuroprotection might include antioxidant, antiapoptotic, antineuroinflammatory and modulation of various cellular and intracellular targets. In in-vivo systems, before reaching to brain, they have to cross barriers like extensive first pass metabolism, intestinal barrier and ultimately blood brain barrier. Different flavonoids have varied pharmacokinetic characteristics, which affect their pharmacodynamic profile. Therefore, brain accessibility of flavonoids is still debatable.
This review emphasized on current trends of research and development on flavonoids, especially in neurodegenerative diseases, possible challenges and strategies to encounter using novel drug delivery system.
Various flavonoids have elicited their therapeutic potential against neurodegenerative diseases, however by using nanotechnology and novel drug delivery systems, the bioavailability of favonoids could be enhanced.
This study bridges a significant opinion on medicinal chemistry, ethanopharmacology and new drug delivery research regarding use of flavonoids in management of neurodegeneration.
Chrysin, a herbal bioactive molecule, exerts a plethora of pharmacological effects, including anti-oxidant, anti-inflammatory, neuroprotective, and anti-cancer. A growing body of evidence has ...highlighted the emerging role of chrysin in a variety of neurological disorders, including Alzheimer's and Parkinson's disease, epilepsy, multiple sclerosis, ischemic stroke, traumatic brain injury, and brain tumors. Based on the results of recent pre-clinical studies and evidence from studies in humans, this review is focused on the molecular mechanisms underlying the neuroprotective effects of chrysin in different neurological diseases. In addition, the potential challenges, and opportunities of chrysin's inclusion in the neurotherapeutics repertoire are critically discussed.
Parkinson's disease (PD) is the second leading neurodegenerative disease that is characterized by severe locomotor abnormalities. Levodopa (L-DOPA) treatment has been considered a mainstay for the ...management of PD; however, its prolonged treatment is often associated with abnormal involuntary movements and results in L-DOPA-induced dyskinesia (LID). Although LID is encountered after chronic administration of L-DOPA, the appearance of dyskinesia after weeks or months of the L-DOPA treatment has complicated our understanding of its pathogenesis. Pathophysiology of LID is mainly associated with alteration of direct and indirect pathways of the cortico-basal ganglia-thalamic loop, which regulates normal fine motor movements. Hypersensitivity of dopamine receptors has been involved in the development of LID; moreover, these symptoms are worsened by concurrent non-dopaminergic innervations including glutamatergic, serotonergic, and peptidergic neurotransmission. The present study is focused on discussing the recent updates in molecular mechanisms and therapeutic approaches for the effective management of LID in PD patients.
DNA methylation, in the mammalian genome, is an epigenetic modification that involves the transfer of a methyl group on the C5 position of cytosine to derive 5-methylcytosine. The role of DNA ...methylation in the development of the nervous system and the progression of neurodegenerative diseases such as Alzheimer's disease has been an interesting research area. Furthermore, mutations altering DNA methylation affect neurodevelopmental functions and may cause the progression of several neurodegenerative diseases. Epigenetic modifications in neurodegenerative diseases are widely studied in different populations to uncover the plausible mechanisms contributing to the development and progression of the disease and detect novel biomarkers for early prognosis and future pharmacotherapeutic targets. In this manuscript, we summarize the association of DNA methylation with the pathogenesis of the most common neurodegenerative diseases, such as, Alzheimer's disease, Parkinson's disease, Huntington diseases, and amyotrophic lateral sclerosis, and discuss the potential of DNA methylation as a potential biomarker and therapeutic tool for neurogenerative diseases.
One of the most prevalent neurodegenerative disorders is Alzheimer's disease (AD). Despite the pervasiveness of AD being considerable, the rates of both diagnosis and therapy are comparatively less ...and still lacking. For the treatment of AD, acetylcholinesterase inhibitors and NMDA receptor antagonists (Memantine) have received clinical approval. The approved drugs are only capable of mitigating the symptoms; however, halting the progression of the disease remains a matter of substantial concern. MicroRNAs (miRs) are a subclass of non-coding single-stranded RNA molecules that target mRNAs to control the expression of genes in certain tissues. Dysregulation in the expression and function of miRs contributes to a neurodegeneration-like pathogenesis seen in Alzheimer's disease (AD), featuring hallmark characteristics such as Aβ aggregation, hyper-phosphorylation of Tau proteins, mitochondrial dysfunction, neuroinflammation, and apoptosis. These factors collectively underpin the cognitive deterioration and learning disabilities associated with AD. According to the research, numerous miRs have considerably different expression patterns in AD patients compared to healthy people. Due to these attributes, miRs prove to be effective diagnostic and therapeutic agents for AD. This review will examine clinical and preclinical data concerning the potential of miRs as diagnostic and therapeutic agents, utilizing various techniques (such as miR antagonists or inhibitors, miR agonists or mimics, miR sponges, and miR antisense oligonucleotides) to target specific pathogenic mechanisms in AD.
During the aging of the global population, the prevalence of neurodegenerative diseases will be continuously growing. Although each disorder is characterized by disease-specific protein ...accumulations, several common pathophysiological mechanisms encompassing both genetic and environmental factors have been detected. Among them, protein arginine methyltransferases (PRMTs), which catalyze the methylation of arginine of various substrates, have been revealed to regulate several cellular mechanisms, including neuronal cell survival and excitability, axonal transport, synaptic maturation, and myelination. Emerging evidence highlights their critical involvement in the pathophysiology of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal dementia–amyotrophic lateral sclerosis (FTD-ALS) spectrum, Huntington’s disease (HD), spinal muscular atrophy (SMA) and spinal and bulbar muscular atrophy (SBMA). Underlying mechanisms include the regulation of gene transcription and RNA splicing, as well as their implication in various signaling pathways related to oxidative stress responses, apoptosis, neuroinflammation, vacuole degeneration, abnormal protein accumulation and neurotransmission. The targeting of PRMTs is a therapeutic approach initially developed against various forms of cancer but currently presents a novel potential strategy for neurodegenerative diseases. In this review, we discuss the accumulating evidence on the role of PRMTs in the pathophysiology of neurodegenerative diseases, enlightening their pathogenesis and stimulating future research.
Epilepsy is one of the most common neurological disorders, characterized by recurrent seizures, resulting from abnormally synchronized episodic neuronal discharges. Around 70 million people worldwide ...are suffering from epilepsy. The available antiepileptic medications are capable of controlling seizures in around 60-70% of patients, while the rest remain refractory. Poor seizure control is often associated with neuro-psychiatric comorbidities, mainly including memory impairment, depression, psychosis, neurodegeneration, motor impairment, neuroendocrine dysfunction, etc., resulting in poor prognosis. Effective treatment relies on early and correct detection of epileptic foci. Although there are currently a few well-established diagnostic techniques for epilepsy, they lack accuracy and cannot be applied to patients who are unsupportive or harbor metallic implants. Since a single test result from one of these techniques does not provide complete information about the epileptic foci, it is necessary to develop novel diagnostic tools. Herein, we provide a comprehensive overview of the current diagnostic tools of epilepsy, including electroencephalography (EEG) as well as structural and functional neuroimaging. We further discuss recent trends and advances in the diagnosis of epilepsy that will enable more effective diagnosis and clinical management of patients.
Psoriasis is a typical dermal condition that has been anticipated since prehistoric times when it was mistakenly implicit in being a variant of leprosy. It is an atypical organ-specific autoimmune ...disorder, which is triggered by the activation of T-cells and/or B-cells. Until now, the pathophysiology of this disease is not completely explicated and still, many research investigations are ongoing. Different approaches have been investigated to treat this dreadful skin disease using various anti-psoriatic drugs of different modes of action through smart drug-delivery systems. Nevertheless, there is no ideal therapy for a complete cure of psoriasis owing to the dearth of an ideal drug-delivery system for anti-psoriatic drugs. The conventional pharmacotherapy approaches for the treatment of psoriasis demand various classes of anti-psoriatic drugs with optimum benefit/risk ratio and insignificant untoward effects. The advancement in nanoscale drug delivery had a great impact on the establishment of a nanomedicine-based therapy for better management of psoriasis in recent times. Nanodrug carriers are exploited to design and develop nanomedicine-based therapy for psoriasis. It has a promising future in the improvement of the therapeutic efficacy of conventional anti-psoriatic drugs. The present manuscript aims to discuss the pathophysiology, conventional pharmacotherapy, and contemporary research in the area of nanoscale topical drug delivery systems for better management of psoriasis including the significance of targeted pharmacotherapy in psoriasis.
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