Treatment Of Neurodegenerative Diseases Research Articles

Commentary on the Obtention of Semi-Synthetic Derivatives from Natural Products for Medicinal Applications: Advances, Challenges, and Perspectives.

Plants have historically been a primary source of medicines due to their diverse molecular and structural composition. Plant metabolism, comprising primary and secondary processes, produces primary metabolites crucial for growth and secondary metabolites, or natural products (NPs), with specific biological functions. These small molecules are instrumental in pharmacology for their ability to penetrate biological barriers and interact with intracellular targets. The structural complexity and limited availability of NPs have led to research focusing on enhancing their diversity through semi-synthesis. In this commentary, examples of various semisynthetic derivatives of NPs obtained through different synthetic strategies, such as organic semi-synthesis or combinatorial chemistry, are cited. Additionally, the importance of developing hybrid molecules based on the combination of two or more distinct pharmacophores is emphasized. This strategy has been widely implemented to obtain new multitarget drugs applicable to the treatment of multifactorial neurodegenerative diseases, where stimulating the cholinergic system by modulating different therapeutic targets is crucial. However, challenges, such as structural complexity, raw material availability, and the need for precise synthetic methods, persist. Innovations in synthetic routes, sustainable harvesting, and biotechnological advances are critical to overcoming these barriers. The integration of omics technologies, green chemistry principles, and global collaboration is essential to maximize the potential of NPs in drug development, ensuring sustainable and efficient production of new therapeutics.

Design of Optogenetic Microimplants for the Treatment of Neurodegenerative Disease

In the context of global aging, neurodegenerative diseases such as Alzheimer’s disease have become important issues in global public health and scientific research. This is due to their soaring incidence, serious impact on patients’ quality of life, and the huge burden they place on families and social economies. However, current treatments, such as drug therapy and deep brain stimulation, have obvious shortcomings. Moreover, there is a lack of precise neuromodulation tools to study the pathogenesis of these diseases In order to solve these problems, optogenetics has attracted attention in recent years, which uses light as a stimulus signal carrier and can realize the detection and control of neurodegenerative diseases at the level of neurons and neural circuits by implanting micro-implants such as μ leds. This review summarize the recent advances in microimplant technology in the fields of optogenetics and neuroscience, and summarize the development and application of optogenetic microimplants for the treatment of neurodegenerative diseases in detail.

Virus-like Particles-Based Vaccine to Combat Neurodegenerative Diseases.

Neurodegenerative diseases are regarded as gradual, incurable conditions with an insidious onset. Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the most prevalent neurodegenerative diseases reported globally. Developing effective treatment strategies for neurodegenerative diseases has remained a primary objective and a huge challenge for researchers. The therapeutic medications that are now approved for the treatment of neurodegenerative diseases merely treat the symptoms; the underlying pathology is not addressed. Therefore, the emergence of novel disease-modifying therapeutic modalities such as immunotherapy has opened a new path in developing effective treatments for neurogenerative diseases. Compared to other types of subunit active vaccines, virus-like particles (VLPs) are considerably more immunogenic as they present dense and repetitive viral antigen epitopes on their surface, which can trigger both humoral and cell-mediated immune responses. They are also a much safer option than the traditional inactivated and live-attenuated vaccines since they are devoid of viral genomes and are, therefore, non-pathogenic and non-infectious. Researchers have turned their attention to VLPs as an active immunotherapy candidate for AD due to the lessons learned from the AN1792 trial. Studies have shown that they effectively induce anti-Aβ, anti-tau, and anti-α-Synuclein antibodies while avoiding T-cell-related immune reactions in animal models of AD and PD. This review compiles the findings of preclinical animal model studies and clinical investigations on VLP-based vaccines for neurogenerative diseases thus far. The technical limitations and potential difficulties associated with the future application of VLP-based vaccines in patients with neurodegenerative diseases have also been covered.

Enhancing drug-target interaction predictions in context of neurodegenerative diseases using bidirectional long short-term memory in male Swiss albino mice pharmaco-EEG analysis

Background and ObjectiveEmerging diseases like Parkinson or Alzheimer's, which are not curable, endanger human mental health and are challenging to research. Drug target interactions (DTI) are pivotal in the screening of candidate drugs and focus on a small pool of drug targets. Electroencephalogram shows the responses to psychotropic medicines in the brain bioelectric activity. Synaptic activity can be analyzed by using Local Field Potential recordings obtained from micro-electrodes implanted in the brain. The aim is to evaluate the effects of drug on brain bioelectric activity and increase the drug classification accuracy. The ultimate goal is to advance our understanding of how drugs affect synaptic activity and open the door to more focused treatment for neurodegenerative diseases. MethodsIn this study, Pharmaco-EEG recordings are processed using Advanced neural network models, particularly Convolutional Neural Networks, to assess the effects of medications. The five different medicines used in this study are Ephedrine, Fluoxetine, Kratom, Morphine, and Saline. The signals observed are local field potential signals. To overcome some limits of DTI prediction, we propose Bidirectional Long Short-Term Memory (LSTM) for the categorization of intracranial EEG (i-EEG) data, departing from standard approaches. Similar EEG patterns are presumably caused by drugs that work by homologous pharmacological pathways, producing similar psychotropic effects. To improve accuracy and reduce training loss, our study introduces a bidirectional LSTM model for classification along with Bayesian optimization ResultsHigh recall, precision, and F1-Scores, particularly a 95% F1-Score for morphine, ephedrine, fluoxetine, and saline, suggest good performance in predicting these drug classes. Kratom produces a somewhat lower recall of 94%, but a high F1-Score of 97% and perfect precision of 1.00. The weighted average F1-Score, macro average, and overall accuracy are all consistently high (around 97%), indicating that the model works well throughout the spectrum of drugs. ConclusionsImproved model performance was demonstrated by using a diversified dataset with five drug categories and bidirectional LSTM boosted with Bayesian optimization for hyperparameter tuning. From earlier limited-category models, it represents a substantial advancement.

Medicinal cannabis delivery systems: A perspective

In recent years, cannabis derivatives have been proposed for the treatment of various medical conditions, including pain, inflammation, epilepsy, sleep disorders, multiple sclerosis, anorexia, schizophrenia, neurodegenerative diseases, nausea, and cancer. While the benefits of cannabis derivatives, primarily cannabinoids, have been demonstrated and continue to be studied, their use presents various challenges associated with their low water solubility, rapid metabolism, erratic and poor bioavailability, and erratic pharmacokinetics, which directly affect their efficacy. In this context, a great deal of research is being carried out to overcome these drawbacks by designing delivery systems capable of improving solubility/bioavailability, potency, and efficacy, while addressing the purity and quality issues required by the pharmaceutical industry. This article aims to critically review the major trends and challenges in designing controlled-release cannabinoid delivery systems and their potential application in the pharmaceutical industry.

In Silico and ADMET Studies of Spiro-Quinazoline Compounds as Acetylcholine Esterase Inhibitors Against Alzheimer's Disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory impairment resulting from the degeneration and death of brain neurons. Acetylcholinesterase (AChE) inhibitors are used in primary pharmacotherapy for numerous neurodegenerative conditions, providing their capacity to modulate acetylcholine levels crucial for cognitive function. Recently, quinazoline derivatives have emerged as a compelling model for neurodegenerative disease treatment, showcasing promising pharmacological features. Their unique structural features and pharmacokinetic profiles have sparked interest in their potential efficacy and safety across diverse neurodegenerative disorders. The exposure of quinazoline derivatives as a potential therapeutic way underscores the imperative for continued research exploration. Their multifaceted mechanisms of action and ability to target various pathways implicated in neurodegeneration offer exciting prospects for developing novel, effective, and well-tolerated treatments. Further investigations into their pharmacological activities and precise therapeutic roles are essential to advance our understanding of neurodegenerative disease pathophysiology and promote the development of modern therapeutic strategies to address this critical medical challenge. Quinazoline derivatives have gained eminent acetylcholinesterase (AChE) inhibitory activity. Their ability to effectively modulate AChE activity makes them promising candidates for treating neurological disorders, particularly Alzheimer's disease (AD). Their intricate molecular structures confer selectivity and affinity for AChE, offering potential for the development of novel therapeutic agents targeting cholinergic pathways. Hence, in this study, we designed, synthesized, and characterized a series of spiro[cycloalakane-1,2'-quinazoline derivatives (1-6) to assess their possible AChE inhibiting ability using docking into the active sites. The AChE inhibitory potential of spiro[cycloalkane-1,2'-quinazoline derivatives (1-6) was explored via docking studies of the AChE active site. The findings revealed significant inhibitory activity and highlighted the promising nature of these derivatives. The synthesized spiro[cycloalkane-1,2'-quinazoline derivatives (1-6) exhibited their notable potential as AChE inhibitors. The observed significant inhibitory activity suggested that these derivatives warrant further exploration as candidates for developing therapeutic agents in AChE inhibitory pathways. This study emphasizes the relevance of quinazoline derivatives in searching for novel treatments for neurological disorders, particularly associated with cholinergic dysfunction, and they could be a useful alternative therapeutic agent.

Omnidirectional improvement of mitochondrial health in Alzheimer's disease by multi-targeting engineered activated neutrophil exosomes

Alzheimer's disease (AD) is one kind of devasting neurodegenerative disorders affecting over 50 million people worldwide. Multi-targeted therapy has emerged as a new treatment for diagnosing and alleviating the pathogenesis process of AD; however, the current strategy is limited by its unsatisfactory efficiency. In our study, engineered activated neutrophil-derived exosomes (MP@Cur-MExo) were developed to improve the mitochondrial function in neurons by targeting and alleviating Aβ-induced neurotoxicity. MP@Cur-MExo are exosomes derived from IL-8-stimulated neutrophils decorated with mitochondria targeting ligand and Aβ targeted ligand modified SPION. Engineered exosomes can be cleaved by matrix metallopeptidase-2, which is overexpressed in the AD brain. Consequently, the released SPION and Curcumin-loaded engineered exosomes collaboratively protected neuron cells against Aβ-induced mitochondrial deficiency. In addition, MP@Cur-MExo effectively accumulated in the inflamed region of AD brain at an early stage, allowing early diagnosis of AD through bimodal (MRI/IVIS) imaging. Importantly, in a mouse model at an early stage of AD, intravenously injected MP@Cur-MExo restored mitochondrial function and reduced Aβ-induced mitochondrial damage, thereby attenuating AD progression. In conclusion, our designed engineered exosomes demonstrated that omnidirectional improvement of mitochondrial function can serve as a novel and practical approach for the diagnosis and treatment of neurodegenerative diseases. This study also reveals a promising therapeutic agent for impeding AD progression for future clinical applications.

Modern Russian drugs for the treatment of neurodegenerative diseases

Neurodegenerative diseases are characterized by progressive death of nerve cells of certain types with concomitant atrophy of the corresponding parts of the spinal cord or brain, which is symptomatically manifested by severe neurological and cognitive impairment. These diseases can manifest at any age and be caused by both genetic predisposition and inflammatory and autoimmune processes. Diseases of this group are a common cause of disability and mortality. Thus, the development of new effective domestic drugs for their treatment is an important task for the healthcare system of the Russian Federation. In this review is devoted to the analysis of Russian original and bioanalog organic and genetically engineered drugs for the treatment of neurodegenerative diseases that have been registered in recent years or are currently undergoing clinical trials in Russia.

Quinic acid contributes to neurogenesis: Targeting Notch pathway a key player in hippocampus

Coordinated proliferation and differentiation of neural stem cells (NSCs) results in continuous neurogenesis. The present study provides novel insights into the Notch intracellular signaling in neuronal cell proliferation, maintenance, migration, and differentiation regulated by naturally based Quinic acid (QA) in primary hippocampal cell culture. Further, this study might help in the discovery and development of lead molecules that can overcome the challenges in the treatment of neurodegenerative diseases. The growth supporting effect of QA was studied using Alamar Blue assay. The migratory potential of QA was evaluated using scratch assay. The in vitro H2O2-induced oxidative stress model was used to upregulate neuronal survival after QA treatment. The RT-qPCR and immunocytochemical analysis were performed for selected markers of Notch signaling to determine the proliferation, differentiation, and maintenance of NSCs at gene and molecular levels. The Mash1 and Ngn2 are the upstream proneural genes of the Notch pathway which were included to evaluate the differentiation of NSCs into mature neurons after treatment with QA.Furthermore, regarding the role of QA in maintaining the pool of NPCs, we used Notch1 and Hes1 markers for proliferation analysis. Also, secondary neuronal markers i.e. Pax6, PCNA, and Mcm2 were included in this study and their gene expression analysis was analyzed following treatment with QA. Based on the study’s results, we suggest that naturally based QA can promote the growth and differentiation of neonatal NSCs residing in hippocampal regions into neuronal lineage. Therefore, we propose that the neurogenic potential of QA can be employed to prevent and treat neurodegenerative diseases.

Incretin Mimetics as Potential Disease Modifying Treatment for Alzheimer's Disease.

Alzheimer's disease is a devastating neurodegenerative condition that exerts a significant global burden. Despite recent efforts, disease modifying therapies remain extremely limited, with a tremendous proportion of patients having to rely on symptomatic treatment only. Epidemiological and pathological overlaps exist between Alzheimer's disease and diabetes mellitus type 2, with people with diabetes mellitus type 2 at a significantly increased risk of developing Alzheimer's disease in the future. Incretin mimetics, also known as GLP-1/GIP receptor agonists, are useful tools licensed for the treatment of diabetes mellitus type 2 which have recently been the subject of news coverage for their off-label use as weight loss medications. Emerging evidence highlights the possible neuroprotective function of incretin mimetics in models of Alzheimer's disease as well as in clinical studies. This review details the pre-clinical and clinical studies that have explored the effectiveness of incretin mimetics to alleviate Alzheimer's disease associated pathology and cognitive impairment, while also highlighting the progress made to examine the effectiveness of these molecules in Parkinson's disease. Should clinical trials prove effective, incretin mimetics may be able to be repurposed and become useful novel tools as disease-modifying treatments for Alzheimer's disease and other neurodegenerative diseases.

The Emerging Role of Phosphodiesterase 5 Inhibition in Neurological Disorders: The State of the Art.

Growing evidence suggests that neuroinflammation is not just a consequence of neurodegeneration in pathologies such as Alzheimer's disease, Parkinson's disease, Huntington's disease or Amyotrophic lateral sclerosis, but it is rather a determinant factor, which plays a pivotal role in the onset and progression of these disorders. Neuroinflammation can affect cells and processes in the central nervous system (CNS) as well as immune cells, and might precede protein aggregation, which is a hallmark of the neurodegenerative process. Standard treatment methods are far from being able to counteract inflammation and delay neurodegeneration. Remarkably, phosphodiesterase 5 inhibitors (PDE5is), which represent potent vasoactive drugs used as a first-line treatment for erectile dysfunction (ED), display important anti-inflammatory effects through cyclic guanosine monophosphate (cGMP) level stabilization. Since PDE5 hydrolyzes cGMP, several studies positioned PDE5 as a therapeutic target, and more specifically, PDE5is as potential alternative strategies for the treatment of a variety of neurological disorders. Indeed, PDE5is can limit neuroinflammation and enhance synaptic plasticity, with beneficial effects on cognitive function and memory. The aim of this review is to provide an overview of some of the main processes underlying neuroinflammation and neurodegeneration which may be potential targets for PDE5is, focusing on sildenafil, the most extensively studied. Current strategies using PDEis for the treatment of neurodegenerative diseases will be summarized.

Designed Nanodrugs for Ultrasonic Removal of Toxic Polyglutamine Aggregates from Neuron Cells.

Clearing of toxic polyglutamine aggregates from neuronal cells is crucial for ameliorating Huntington's disease. However, such clearance is challenging, requiring the targeting of affected neuron cells in the brain, followed by the removal of polyglutamine from cells. Here we report a designed nanodrug that can be used for the ultrasound-based removal of toxic polyglutamine aggregates from neuron cells. The nanodrug is composed of a sonosensitizer molecule, chlorin e6- or protoporphyrin IX-loaded polymer micelle of 20-30 nm in size that rapidly delivers the sonosensitizer into the cell nucleus. Ultrasound exposure of these cells generates singlet oxygen in the nucleus/perinuclear region that induces strong autophagic flux and clears toxic polyglutamine aggregates from cells. It has been demonstrated that the nanodrug and ultrasound treatment can enhance the cell survival against polyglutamine aggregates by 4 times. This result suggests that the nanodrug can be designed for focused ultrasound-based wireless treatment of various neurodegenerative diseases.

The Current Treatment for Neurodegenerative Diseases

Neurodegenerative diseases (NDs) refer to dysfunction of central nerve system, characterized by progressive loss of neuronal structure and function, ultimately resulting in decline in patients memory, motor ability, language and intelligence. The typical NDs include age related diseases like Aleimers disease (AD) and genetic diseases such as Huntingtons diseases (HD) and amyotrophic lateral sclerosis (ALS). NDs impose heavy economic burden and suffer to the enormous patients over the world, however, many types of NDs do not have a cure; existing treatments only aim to improve their symptoms. Under that condition, Gene therapy has shown potential for transporting some genetic products into the cells and correct faulty genes. Over the years, research have highlighted the promise of gene therapies using AAV vector in treating NDs. At the same time, a number of emerging therapeutic technologies for neurodegenerative diseases, such as epigenetic interventions through acetylation/deacetylation, gene therapies that target specific mRNAs or non-coding RNAs, and photo biomodulation therapies that can act on brain tissue, are also being studied. In this discussion, we explore the historical, present, and future outlook of gene therapies for neurodegenerative conditions.

Modelling human neuronal catecholaminergic pigmentation in rodents recapitulates age-related neurodegenerative deficits

One key limitation in developing effective treatments for neurodegenerative diseases is the lack of models accurately mimicking the complex physiopathology of the human disease. Humans accumulate with age the pigment neuromelanin inside neurons that synthesize catecholamines. Neurons reaching the highest neuromelanin levels preferentially degenerate in Parkinson’s, Alzheimer’s and apparently healthy aging individuals. However, this brain pigment is not taken into consideration in current animal models because common laboratory species, such as rodents, do not produce neuromelanin. Here we generate a tissue-specific transgenic mouse, termed tgNM, that mimics the human age-dependent brain-wide distribution of neuromelanin within catecholaminergic regions, based on the constitutive catecholamine-specific expression of human melanin-producing enzyme tyrosinase. We show that, in parallel to progressive human-like neuromelanin pigmentation, these animals display age-related neuronal dysfunction and degeneration affecting numerous brain circuits and body tissues, linked to motor and non-motor deficits, reminiscent of early neurodegenerative stages. This model could help explore new research avenues in brain aging and neurodegeneration.

Nitric Oxide Signaling and Sensing in Age-Related Diseases.

Nitric oxide (NO) is a key signaling molecule involved in numerous physiological and pathological processes within the human body. This review specifically examines the involvement of NO in age-related diseases, focusing on the cardiovascular, nervous, and immune systems. The discussion delves into the mechanisms of NO signaling in these diseases, emphasizing the post-translational modifications of involved proteins, such as S-nitrosation and nitration. The review also covers the dual nature of NO, highlighting both its protective and harmful effects, determined by concentration, location, and timing. Additionally, potential therapies that modulate NO signaling, including the use of NO donors and nitric oxide synthases (NOSs) inhibitors in the treatment of cardiovascular, neurodegenerative, and oncological diseases, are analyzed. Particular attention is paid to the methods for the determination of NO and its derivatives in the context of illness diagnosis and monitoring. The review underscores the complexity and dual role of NO in maintaining cellular balance and suggests areas for future research in developing new therapeutic strategies.

Effects of Leaf Extracts from Genetic Resource of Capsicum spp. on Neuroprotection and Anti-Neuroinflammation in HT22 and in BV2 Cells.

To develop functional varieties of Capsicum spp. leaves, 40 genetic resources were collected and extracted with 30% aqueous-fermented ethanol. We investigated the protective effects of extracts from 40 genetic resources of Capsicum spp. on glutamate-induced HT22 and LPS-induced BV2 cells. The results showed that the five extracts exhibited cell-protective activities. We also investigated the anti-inflammatory effects of these five extracts on LPS-induced BV2 cell neuroinflammation and found that 23OM18 exhibited superior anti-inflammatory effects. We further investigated the protective activity and anti-inflammatory mechanisms of 23OM18 in these two cell models. In addition, the profiles of 16 metabolites were compared between the representative accessions and among the five genetic resources using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). The results showed that 23OM18 protected HT22 cells by inhibiting reactive oxygen species generation and regulating the MAPK-JNK signaling pathway, thereby reducing LPS-induced BV2 cell neuroinflammation by regulating the NF-κB and MAPK signaling pathways. Based on these results, 23OM18 has the potential to be developed as a functional food for the treatment of neurodegenerative diseases.

A computational and machine learning approach to identify GPR40-targeting agonists for neurodegenerative disease treatment.

The G protein-coupled receptor 40 (GPR40) is known to exert a significant influence on neurogenesis and neurodevelopment within the central nervous system of both humans and rodents. Research findings indicate that the activation of GPR40 by an agonist has been observed to promote the proliferation and viability of hypothalamus cells in the human body. The objective of the present study is to discover new agonist compounds for the GPR40 protein through the utilization of machine learning and pharmacophore-based screening techniques, in conjunction with other computational methodologies such as docking, molecular dynamics simulations, free energy calculations, and investigations of the free energy landscape. In the course of our investigation, we successfully identified five unreported agonist compounds that exhibit robust docking score, displayed stability in ligand RMSD and consistent hydrogen bonding with the receptor in the MD trajectories. Free energy calculations were observed to be higher than control molecule. The measured binding affinities of compounds namely 1, 3, 4, 6 and 10 were -13.9, -13.5, -13.4, -12.9, and -12.1 Kcal/mol, respectively. The identified molecular agonist that has been found can be assessed in terms of its therapeutic efficacy in the treatment of neurological diseases.

Evaluation of <i>Saussurea lappa</i> on Oxidative Stress and Cognition in Aluminium-induced Alzheimer’s Disease Rats

Background: Oxidative stress and neurodegenerative illnesses, such as Alzheimer's disease (AD), are closely associated. There has been a lot of thought put into finding medicinal plants with nootropic properties to slow the onset and course of AD. Objective: The study aimed to evaluate the methanolic extract of Saussurea lappa clarke (MESC) on oxidative stress and cognitive ability induced by aluminium exposure. Methods: Wistar albino rats were chosen for the study. About 30 animals were selected and grouped into 5 with 6 animals in each group. Group I served as control, group II served as disease induced (Aluminium-induced), group III, IV and V were administered with standard drug – Donepezil Hcl, and MESC at two doses – 200 and 400 mg/kg. The behavioural studies were examined by using certain apparatus like Passive Avoidance (PA) test, Elevated Plus Maze, Y- Maze and Actophotometer. Determination of anti-oxidant enzymes – Catalase (CAT) and thiobarbituric acid reactive substances (TBARS) along with acetylcholinesterase (AChE) levels which was done in rat’s brain homogenate. Results: In the PA test, administration of MESC at doses of 200 and 400 mg/kg significantly (**p< 0.01) lengthened step-through latency (STL) in rats on day 30 compared to the positive control group. Animals at MESC (200 & 400 mg/kg) showed noticeably higher memory retention (MR) rates as compared to the disease-control group. Additionally, administration of MESC (200 and 400 mg/kg) significantly (**p< 0.01) raised CAT and declined the concentration of TBARS. AChE concentration was significantly (**p< 0.01) reduced at the dose of MESC at 200 and 400 mg/kg as compared to the positive control group. Conclusion: The present study showed that MESC had a strong nootropic effect on brain antioxidant indicators and cognitive function in rats exposed to aluminium-induced oxidative stress and cognitive impairment. These findings may be investigated in the treatment of neurodegenerative diseases, including AD.

Therapeutic Potential of Capsaicin in Various Neurodegenerative Diseases with Special Focus on Nrf2 Signaling.

Neurodegenerative disease is mainly characterized by the accumulation of misfolded proteins, contributing to mitochondrial impairments, increased production of proinflammatory cytokines and reactive oxygen species, and neuroinflammation resulting in synaptic loss and neuronal loss. These pathophysiological factors are a serious concern in the treatment of neurodegenerative diseases. Based on the symptoms of various neurodegenerative diseases, different treatments are available, but they have serious side effects and fail in clinical trials, too. Therefore, treatments for neurodegenerative diseases are still a challenge at present. Thus, it is important to study an alternative option. Capsaicin is a naturally occurring alkaloid found in capsicum. Besides the TRPV1 receptor activator in nociception, capsaicin showed a protective effect in brain-related disorders. Capsaicin also reduces the aggregation of misfolded proteins, improves mitochondrial function, and decreases ROS generation. Its antioxidant role is due to increased expression of an nrf2-mediated signaling pathway. Nrf2 is a nuclear erythroid 2-related factor, a transcription factor, which has a crucial role in maintaining the normal function of mitochondria and the cellular defense system against oxidative stress. Intriguingly, Nrf2 mediated pathway improved the upregulation of antioxidant genes and inhibition of microglial-induced inflammation, improved mitochondrial resilience and functions, leading to decreased ROS in neurodegenerative conditions, suggesting that Nrf2 activation could be a better therapeutic approach to target pathophysiology of neurodegenerative disease. Therefore, the present review has evaluated the potential role of capsaicin as a pharmacological agent for the treatment and management of various neurodegenerative diseases via the Nrf2-mediated signaling pathway.

Designing and Formulation of Nanocarriers for "Alzheimer's and Parkinson's" Early Detection and Therapy.

The potential of nanotechnology in advancing the diagnosis and treatment of neurodegenerative diseases is explored in this comprehensive literature review. The findings of these studies suggest that nanotechnology has the capacity to improve existing therapeutic approaches, create novel and safe compounds, and develop more precise imaging techniques and diagnostic methods for neurodegenerative diseases. With the emergence of the nanomedicine era, a new and innovative approach of diagnosing and treating these conditions has been introduced. Notably, the researchers' development of a nanocarrier drug delivery tool demonstrates immense potential compared to conventional therapy, as it maximizes therapeutic efficacy and minimizes undesirable as side effects.