Treatment Of Neurodegenerative Diseases Research Articles

Targeting chaperone-mediated autophagy in neurodegenerative diseases: mechanisms and therapeutic potential.

The pathological hallmarks of various neurodegenerative diseases including Parkinson's disease and Alzheimer's disease prominently feature the accumulation of misfolded proteins and neuroinflammation. Chaperone-mediated autophagy (CMA) has emerged as a distinct autophagic process that coordinates the lysosomal degradation of specific proteins bearing the pentapeptide motif Lys-Phe-Glu-Arg-Gln (KFERQ), a recognition target for the cytosolic chaperone HSC70. Beyond its role in protein quality control, recent research underscores the intimate interplay between CMA and immune regulation in neurodegeneration. In this review, we illuminate the molecular mechanisms and regulatory pathways governing CMA. We further discuss the potential roles of CMA in maintaining neuronal proteostasis and modulating neuroinflammation mediated by glial cells. Finally, we summarize the recent advancements in CMA modulators, emphasizing the significance of activating CMA for the therapeutic intervention in neurodegenerative diseases.

Delivery of Neuroregenerative Proteins to the Brain for Treatments of Neurodegenerative Brain Diseases

Neurodegenerative brain diseases such as Alzheimer’s disease (AD), multiple sclerosis (MS), and Parkinson’s disease (PD) are difficult to treat. Unfortunately, many therapeutic agents for neurodegenerative disease only halt the progression of these diseases and do not reverse neuronal damage. There is a demand for finding solutions to reverse neuronal damage in the central nervous system (CNS) of patients with neurodegenerative brain diseases. Therefore, the purpose of this review is to discuss the potential for therapeutic agents like specific neurotrophic and growth factors in promoting CNS neuroregeneration in brain diseases. We discuss how BDNF, NGF, IGF-1, and LIF could potentially be used for the treatment of brain diseases. The molecule’s different mechanisms of action in stimulating neuroregeneration and methods to analyze their efficacy are described. Methods that can be utilized to deliver these proteins to the brain are also discussed.

Ferroptosis as a Therapeutic Target in Neurodegenerative Diseases: Exploring the Mechanisms and Potential of Treating Alzheimer's Disease and Parkinson's Disease.

Amidst the rising global burden of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, there is an urgent need for novel therapeutic strategies to combat these debilitating conditions. These diseases are characterized by progressive neural dysfunction leading to cognitive impairments, for which current therapeutic strategies remain palliative at best. Recently, the discovery of ferroptosis, a novel cell death mode that is different from apoptosis and autophagy, has opened new avenues in the field of cognitive research. With in-depth research on ferroptosis, the clinical significance of iron homeostasis disorders and lipid peroxidation in the occurrence, development, and treatment of neurodegenerative diseases are gradually becoming apparent. This study aims to elucidate the roles of ferroptosis in the context of neurodegeneration and to explore its potential as a therapeutic target. By unraveling the intricate relationship between iron homeostasis disorders, oxidative damage, and lipid metabolism disturbances in these diseases, new intervention targets are revealed. It offers a new dimension to the management of neurocognitive impairments in Alzheimer's and Parkinson's diseases. The implications of these findings extend beyond just Alzheimer's and Parkinson's diseases. They also have relevance with other neurological conditions characterized by oxidative stress and iron dysregulation. This review contributes to increased knowledge of ferroptosis and provides a foundational understanding that could lead to the development of innovative therapeutic strategies. Ultimately, it may alleviate the development of neurodegenerative diseases and improve cognitive function by preventing ferroptosis, which has not only academic significance but also potential clinical significance.

In Silico and In Vitro Evaluation of Quinoline Derivatives as Potential Inhibitors of AChE, BACE1, and GSK3β for Neurodegenerative Diseases Treatment.

Neurodegenerative diseases are characterized by the structural and functional loss of neurons, affecting populations worldwide. Enzymes like acetylcholinesterase (AChE), beta-site APP cleaving enzyme-1 (BACE1), and glycogen synthase kinase 3-beta (GSK3β), contribute to their development. This study explores in silico and in vitro assays of quinoline analogues as potential inhibitors of these enzymes. In silico analyses highlighted derivative SQ6 as the most potent inhibitor for all proteins. In vitro assays confirmed that the quinoline derivatives had a modulating action on the three targets. SQ6 showed a significant AChE inhibition of 94.6%. Regarding the inhibition of GSK3β and BACE1, derivatives SQ6-SQ9, with the quinoline linked to the sulfonamide nitrogen, showed inhibition values above 40%. SQ7 and SQ9 were not considered cytotoxic for cell proliferation in human glioblastoma, and SQ6 did not show cytotoxicity at 7.8 and 3.9 µg mL-1. In murine fibroblasts, SQ6 presented a result similar to that observed for cell proliferation in human glioblastoma, while SQ7 and SQ9 were non-cytotoxic below 62.5 µg mL-1. These findings underscore compound SQ6 as the first potential multitarget enzyme inhibitor for treating neurodegenerative diseases.

Response to amoxicillin and perampanel in infantile Alexander disease.

Type I Alexander disease (AxD) presents with paroxysmal neurodegeneration, refractory epilepsy, and encephalopathy in the first years of life and is associated with a poor prognosis. Although there is no treatment, mild symptomatic improvement has been reported in one case of adult Alexander treated with ceftriaxone, given its interaction with the mutant glial fibrillary acid protein (GFAP) responsible for the disease's pathogenesis. We describe a patient presenting with irritability starting at 2 months of age, initially attributed to gastroesophageal reflux. A ventriculoperitoneal shunt was placed at 3 months of age due to hydrocephalus secondary to aqueduct stenosis detected through an MRI scan, but the irritability persisted. At 5 months, a new brain MRI was performed due to irritability worsening, onset of abnormal ocular movements and seizures. In addition genetic testing was performed. AxD was diagnosed due to the mutation c.716G>A (p.Arg239His) in GFAP. Since irritability had worsened and had not responded to levomepromazine, treatment with amoxicillin (80 mg/kg/day) was attempted to modulate glutamate levels. The patient showed a striking improvement of irritability in 48 h that persisted over the next months. The patient had frequent daily seizures which did not respond to valproate, clonazepam, or phenobarbital. Perampanel, a postsynaptic AMPA receptor antagonist, was added to phenobarbital and he was seizure free for more than 3 months. Drugs modulating glutamate levels in the central nervous system, including β-lactam antibiotics and perampanel, may have an important role in the symptomatic treatment of AxD and other neurodegenerative diseases where glutamatergic excitotoxicity is a pathogenic determinant. PLAIN LANGUAGE SUMMARY: Alexander disease is a rare and serious condition that affects the brain, often leading to neurodegeneration (brain damage), seizures, and other problems in early childhood. The disease is caused by a mutation in a gene called GFAP. There is no cure, and current treatments mainly focus on relieving symptoms. This article discusses the case of a baby who showed signs of irritability and seizures from a young age. The baby was diagnosed with Alexander disease after brain scans and genetic testing. Despite treatment with various drugs, the baby continued to experience seizures and irritability. The doctors decided to try amoxicillin, a common antibiotic, because of its potential to help control the disease by affecting a brain chemical called glutamate. Surprisingly, the baby's irritability improved within 2 days of starting amoxicillin, and the improvement lasted for several months. However, the seizures persisted until another medication, perampanel, was added. This combination controlled the baby's seizures for over 3 months. Unfortunately, the baby passed away at 13 months due to complications from the disease. However, doctors believe that drugs like amoxicillin and perampanel could be promising treatments for managing symptoms of Alexander disease and other similar brain conditions in the future, especially where excess glutamate plays a role in the damage. This case suggests that these treatments may help control irritability and seizures, offering hope for better management of this challenging disease.

Neural Stem Cell Therapy for Alzheimer’s Disease: A-State-of-the-Art Review

Alzheimer’s disease (AD) is a brain disorder that is more prevalent in developed nations and remains one of most intractable conditions so far. It is characterized by a gradual onset, a prolonged progression, and an unclear pathophysiology. At the present time, there are no effective treatments available for the disease. However, human neural stem cells (hNSCs) have the capacity to substitute lost neurons in a functional manner, strengthen synaptic networks that have been compromised, and repair the damaged brain. Due to the unavailability of restorative therapeutics, there is a significant global burden on the economy. When it comes to the treatment of neurodegenerative diseases, NSCs provide a potentially game-changing approach to treating Alzheimer’s disease. Through the delivery of trophic factors that promote the viability and regeneration of lost neurons in experimental animals suffering from neurodegenerative disorders, these treatments have the potential to facilitate beneficial recuperation. Positive restorative outcomes may be achieved in a variety of ways, including the replacement of lost cells, the combining of cells, the secretion of neurotrophic factors, the formation of endogenous stem cells, and transdifferentiation. Conversely, there are obstacles that need to be overcome before NSC-based treatments can be used in clinical settings. This review article discusses current developments in the use of neural stem cells (NSCs) for the treatment of Alzheimer’s disease (AD). In addition, we highlight the difficulties and opportunities that are involved with the use of neural stem cell transplant treatment for Alzheimer’s disease.

Prolactin protects hippocampal neurons against H2O2-induced neurotoxicity by suppressing BAX and NOX4 via the NF-κB signaling pathway.

Reactive oxygen species (ROS) are physiological byproducts of neuronal metabolism. However, an imbalance between ROS generation and antioxidant capacity, often driven by dysregulated pro-oxidant enzymes like nicotinamide adenine dinucleotide phosphate oxidases (NOX), can result in deleterious oxidative stress. This oxidative stress is a critical factor in the pathogenesis of neurodegenerative diseases. While interventions with broad-spectrum antioxidants have demonstrated limited efficacy, the modulation of endogenous antioxidant mechanisms presents a promising therapeutic avenue. Here, we investigated the potential of the neuroprotective hormone prolactin to mitigate oxidative stress and subsequent neuronal cell death. Prolactin protected primary mouse hippocampal neurons from hydrogen peroxide (H2O2)-induced oxidative damage. Prolactin reduced ROS levels, lipid peroxidation, and apoptosis, and its effects were occluded by a specific prolactin receptor antagonist (G129R-hPRL). Mechanistically, prolactin suppressed H2O2-induced mRNA upregulation of pro-oxidative Nox4 and pro-apoptotic Bax. Moreover, prolactin induced nuclear factor kappa B (NF-κB) nuclear translocation, and the inhibition of the NF-κB signaling pathway abolished the neuroprotective and transcriptional effects of prolactin, indicating its central role in prolactin-mediated protection. Our findings indicate that prolactin exerts potent antioxidant and neuroprotective effects by modulating the expression of Nox4 and Bax, thereby reducing ROS generation and neuronal apoptosis. This study underscores the therapeutic potential of prolactin in attenuating oxidative stress and suggests a possible role in the treatment of neurodegenerative diseases.

Network medicine informed multiomics integration identifies drug targets and repurposable medicines for Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a devastating, immensely complex neurodegenerative disease by lack of effective treatments. We developed a network medicine methodology via integrating human brain multi-omics data to prioritize drug targets and repurposable treatments for ALS. We leveraged non-coding ALS loci effects from genome-wide associated studies (GWAS) on human brain expression quantitative trait loci (QTL) (eQTL), protein QTL (pQTL), splicing QTL (sQTL), methylation QTL (meQTL), and histone acetylation QTL (haQTL). Using a network-based deep learning framework, we identified 105 putative ALS-associated genes enriched in known ALS pathobiological pathways. Applying network proximity analysis of predicted ALS-associated genes and drug-target networks under the human protein-protein interactome (PPI) model, we identified potential repurposable drugs (i.e., Diazoxide and Gefitinib) for ALS. Subsequent validation established preclinical evidence for top-prioritized drugs. In summary, we presented a network-based multi-omics framework to identify drug targets and repurposable treatments for ALS and other neurodegenerative disease if broadly applied.

The activation of inflammatory responses in the brain is potentiated by over-expressing acetylcholinesterase in myeloid lineage of transgenic mice.

Acetylcholinesterase (AChE) has functions in neuroinflammation, beyond its classical role in neurotransmission. Understanding the role of AChE in neuroinflammation is of great significance, as it highlights the potential therapeutic targets for the treatment of neurodegenerative diseases. In an invitro study, the expression of AChE was up-regulated in lipopolysaccharide (LPS)-induced microglia/macrophage and contrarily potentiated the inflammatory responses via disturbing the cholinergic anti-inflammatory pathway (CAP). However, the regulation of AChE in neuroinflammation has not been revealed invivo yet. Here, we aim to uncover the inflammatory roles of microglial AChE in LPS-induced neuroinflammation by using the conditional AChE over-expression mouse model. AChE was specifically over-expressed in the myeloid cell linkage of mouse by applying CRISPR/cas9 combined with Cre-LoxP system. LPS was intraperitoneally injected into the mice to induce inflammation. The results showed that the inflammation, induced by LPS, was aggravated in the brain of transgenic mice having over-expression of AChE in microglia. The expressions of pro-inflammatory cytokines were robustly up-regulated in the brains of LPS-treated transgenic mice, as compared to the LPS-treated wildtypes. In parallel, the activations of microglia and astrocytes in hippocampus were enhanced significantly in AChE transgenic mice. Transcriptomics analysis further confirmed the severer inflammation in the transgenic mice than the wildtype after LPS administration. These findings shed light on the regulation of microglial AChE in neuroinflammation invivo for the first time, presenting another angle to understand the role of AChE in neurodegenerative diseases.

Proteomic Alteration in Catalpol Treatment of Alzheimer's disease by regulating HSPA5/ GPX4

Alzheimer's disease (AD), a chronic and progressive neurodegenerative disease, is characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles. Conventional anti-AD drugs exhibit high toxicity and adversely impact patients' quality of life. Therefore, novel treatments for AD are urgently required. In recent years, targeting ferroptosis through the modulation of lipid oxidation has emerged as a new approach in the treatment of neurodegenerative diseases. Catalpol, an iridoid glycoside isolated from the roots of Rehmannia glutinosa, has exhibited anti-inflammatory, antioxidant, and neuroprotective properties. Therefore, in this study, we investigated the protective effects and associated underlying mechanisms of catalpol in an APP/PS1 AD mouse model. Catalpol treatment significantly improved the cognitive capabilities and decreased Aβ1-40 and Aβ1-42 levels in mice. Morphological testing revealed that catalpol prevented neuronal loss and reduced mitochondrial swelling in the hippocampal CA1 region. Proteomic studies identified 2,495 hippocampus proteins whose expression was associated with the mechanism of catalpol treatment, including 44 ferroptosis-related proteins. Bioinformatic analysis revealed that catalpol significantly increased the protein levels of HSPA5 and GPX4 in the hippocampus. Additionally, catalpol modulated biological pathways related to apoptosis, cytokine-mediated signaling, and ferroptosis. The considerable upregulation of HSPA5 and GPX4 with catalpol was further confirmed through western blotting. Catalpol exhibited neuroprotective effects through a variety of mechanisms. Among these, HSPA5 and GPX4, associated with ferroptosis, may play key roles in AD pathogenesis, and present promising therapeutic targets.

Idebenone Attenuates Diabetic Retinopathy by Modulating Autophagy Via Targeting Akt Signaling.

Diabetic Retinopathy (DR) is a common microvascular issue caused by diabetes. Idebenone (IDE) is a coenzyme Q10 analog and antioxidant that has been utilized in the treatment of neurodegenerative diseases. Our goal was to investigate how IDE might treat diabetic retinopathy. An in vivo DR model was established by injecting a single dose of streptozotocin (STZ). Rats were treated with IDE, and their vascular function was measured by ultrasound. The retina structure was checked by haematoxylin and eosin (HE) staining. The expression of biomarkers of autophagy and apoptosis was measured by western blotting assay. The retina endothelial cell line RF/6A was stimulated with high glucose (HG) and treated with IDE. Cell proliferation and apoptosis were assessed using the Edu assay, TUNEL assay, and flow cytometry, respectively. Reduced peak systolic velocity (PSV), mean velocity (MV), end-diastolic velocity (EDV), and increased pulsatility index (PI) and resistance index (RI) were observed in diabetic rats; however, these traits were reversed by IDE therapy. IDE alleviated the STZ-induced disordered retina structure. The IDE administration suppressed DR-induced apoptosis and autophagy both in vivo and in vitro. IDE suppressed the activation of Phosphatidylinositol 3 kinase (PI3K) signaling. Activation of PI3K abolished the IDE-alleviated retina damage and cell death. IDE regulated the autophagy of retina cells to alleviate diabetic retinopathy via regulating the PI3K signaling pathway.

Development of tau phosphorylation-targeting therapies for the treatment of neurodegenerative diseases

Development of tau phosphorylation-targeting therapies for the treatment of neurodegenerative diseases

Neuroprotective effects of GLP-1 receptor agonists in neurodegenerative Disorders: A Large-Scale Propensity-Matched cohort study

BackgroundGLP-1 receptor agonists, traditionally used for treating type 2 diabetes mellitus and obesity, have demonstrated anti-inflammatory properties. However, their potential neuroprotective effects in neurodegenerative disorders remain unclear. ObjectiveTo evaluate the impact of GLP-1 receptor agonists on the risk of developing various neurodegenerative conditions in obese patients. MethodsThis comprehensive retrospective cohort study analyzed data from 5,307,845 obese adult patients across 73 healthcare organizations in 17 countries. Propensity score matching was performed, resulting in 102,935 patients in each cohort. We compared the risk of developing neurodegenerative disorders between obese patients receiving GLP-1 receptor agonist therapy and those who were not. ResultsObese patients treated with GLP-1 receptor agonists showed significantly lower risks of developing Alzheimer’s disease (RR = 0.627, 95 %CI = 0.481–0.817), Lewy body dementia (RR = 0.590, 95 %CI = 0.462–0.753), and vascular dementia (RR = 0.438, 95 %CI = 0.327–0.588). The risk reduction for Parkinson’s disease was not statistically significant overall (RR = 0.784, 95 %CI = 0.580–1.058) but was significant for semaglutide users (RR = 0.574, 95 %CI = 0.369–0.893). Semaglutide consistently showed the most pronounced protective effects across all disorders. Additionally, a significant reduction in all-cause mortality was observed (HR = 0.525, 95 %CI = 0.493–0.558). ConclusionThis study provides evidence that the effects of GLP-1 receptor agonists may extend beyond their known metabolic and cardioprotective benefits to include neuroprotection, associated with a decreased risk of developing various neurodegenerative disorders. These findings suggest the potential for expanding the therapeutic applications of GLP-1 receptor agonists to improve neurocognitive outcomes. Further research is warranted to elucidate the mechanisms underlying these neuroprotective effects and to explore their clinical applications in neurodegenerative disease prevention and treatment.

Advancements in Targeting Ion Channels for the Treatment of Neurodegenerative Diseases

Advancements in Targeting Ion Channels for the Treatment of Neurodegenerative Diseases

Evaluation of Rhus Tox, a homeopathic formulation for treatment of Parkinson’s and Alzheimer’s disease: a network pharmacology and ex-vivo approach

Rhus toxicodendron, commonly known as Rhus tox, is a potent homeopathic medication widely used in the treatment of rheumatoid arthritis and is claimed to have potential benefits for neurodegenerative disorders. Given the ability of homeopathic medications to address the root causes of diseases, our study aimed to evaluate Rhus tox for Parkinson’s Disease (PD) and Alzheimer’s Disease (AD) using in-silico, ex-vivo, and network pharmacology approaches to obtain comprehensive information on its multi-component and multi-target effects. Phytoconstituents of Rhus tox were collected from PubMed and screened for ADMET properties. Targets for these constituents were predicted using the Binding Database and DisGeNET, resulting in 61 targets for Parkinsonism and 85 targets for alzhiemer’s disease. Protein-protein interactions (PPIs) were analysed using the STRING database. A Venn diagram was constructed for all these targets, and 5 out of 13 common targets were selected for docking studies. From these analyses, kaempferol and quercetin were identified as promising neuroprotective agents with good blood-brain barrier (BBB) permeation. The docking studies validated these predictions as most of the constituents showed good binding affinity with EGFR, SNCA and MAO-B. It was further validated using MAO inhibition assay, in which Quercetin was found to be highly efficacious, with an IC50 value of 32.69 μg/mL among the other flavonoids studied for MAO inhibition assay. The Rhus Tox also showed MAO inhibition assay similar to the standard seligiline. To conclude, we can propose that Rhus Tox primarily acts on the dopaminergic pathway, serotonergic pathway, and EGFR signaling pathway. Further in vitro and in vivo studies are needed to confirm the mechanism action and efficacy of Rhus Tox for treatment of neurodegenerative diseases.

Melissa officinalis Regulates Lipopolysaccharide-Induced BV2 Microglial Activation via MAPK and Nrf2 Signaling.

Neuroinflammation and microglial activation play critical roles in neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Modulating microglial activation may help prevent the progression of these disorders. This study aimed to investigate the effects and mechanisms of Melissa officinalis ethanol extract on lipopolysaccharide (LPS)-induced microglial activation in BV2 cells. Cell viability and nitric oxide (NO) production were assessed using MTT assay and Griess reagent, while inflammatory cytokine levels were measured by qPCR. Key inflammatory pathways, including MAPK, TLR4, and antioxidant biomarkers, were analyzed through western blot and immunofluorescence. Rosmarinic acid content in M. officinalis was determined using high-performance liquid chromatography (HPLC). The results demonstrated that M. officinalis ethanol extract significantly inhibited LPS-induced NO production and reduced inflammatory cytokine expression. Additionally, it downregulated inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TLR4, NF-κB, and MAPK signaling pathways (p38, JNK, ERK), while increasing the expression of antioxidant markers, including Nrf2, HO-1, catalase, and SOD2. In conclusion, M. officinalis ethanol extract exerts neuroprotective effects by modulating inflammation and enhancing antioxidant defenses, suggesting its potential in the prevention and treatment of inflammation-related neurodegenerative diseases.

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.