Progressive Neurological Disorder Research Articles

Gut Microbiota as a Modifier of Huntington's Disease Pathogenesis.

Huntingtin (HTT) protein is expressed in most cell lineages, and the toxicity of mutant HTT in multiple organs may contribute to the neurological and psychiatric symptoms observed in Huntington's disease (HD). The proteostasis and neurotoxicity of mutant HTT are influenced by the intracellular milieu and responses to environmental signals. Recent research has highlighted a prominent role of gut microbiota in brain and immune system development, aging, and the progression of neurological disorders. Several studies suggest that mutant HTT might disrupt the homeostasis of gut microbiota (known as dysbiosis) and impact the pathogenesis of HD. Dysbiosis has been observed in HD patients, and in animal models of the disease it coincides with mutant HTT aggregation, abnormal behaviors, and reduced lifespan. This review article aims to highlight the potential toxicity of mutant HTT in organs and pathways within the microbiota-gut-immune-central nervous system (CNS) axis. Understanding the functions of Wild-Type (WT) HTT and the toxicity of mutant HTT in these organs and the associated networks may elucidate novel pathogenic pathways, identify biomarkers and peripheral therapeutic targets for HD.

Obesity aggravates neuroinflammatory and neurodegenerative effects of bisphenol A in female rats

Bisphenol A (BPA), a common plasticizer, is categorized as a neurotoxic compound and its impact on individuals exhibits sex-linked variations. Several biological and environmental factors impact the degree of toxicity. Moreover, nutritional factors have profound influence on toxicity outcome. BPA has been demonstrated to be an obesogen. However, research on the potential role of obesity as a confounding factor in BPA toxicity is lacking. We studied the neurodegenerative effects in high-fat diet (HFD)-induced obese female rats after being exposed with BPA (10 mg/L via drinking water for 90 days). Four groups were taken in this study – Control, HFD, HFD + BPA and BPA. Cognitive function was evaluated through novel object recognition (NOR) test. Inflammatory changes in brain, and changes in hormonal level, lipid profile, glucose tolerance, oxidative stress and antioxidants were also determined. HFD + BPA group rats showed a significant decline in NOR test. The cerebral cortex (CC) of the brain showed increased neurodegenerative changes as measured by microtubule associated protein-2 (MAP-2) accompanied by histopathological confirmation. The increased level of neuroinflammation was demonstrated by microglial activation (Iba-1) and protein expression of nuclear factor– kappa B (NF-КB) in the brain. Obesity also caused significant (p < 0.05) increase in lipid peroxidation accompanied by reduced activities of antioxidant enzymes (glutathione S-transferase, catalase and glutathione peroxidase) and decrease in reduced-glutathione (p < 0.05) when compared to non-obese rats with BPA treatment. Overall, study revealed that obesity serves as a risk factor in the toxicity of BPA which may exacerbate the progression of neurological diseases.

Analysis of the sodium pump subunit ATP1A3 in glioma patients: Potential value in prognostic prediction and immunotherapy

The ATP1A3 gene is associated with the development and progression of neurological diseases. However, the pathological function and therapeutic value of ATP1A3 in glioblastoma (GBM) remains unknown. In this study, we tried to explore the correlation between the ATP1A3 gene expression and immune features in GBM samples. We found that ATP1A3 gene expression levels showed significant negative correlation with immune checkpoints such as PD-L1, CTLA-4 and IDO1. Next, ATP1A3 gene expression levels showed significant negative correlation with the anti-cancer immune cell process, the immune score and stromal score. By grouping ATP1A3 expression levels, we found that that immunomodulator-related genes and tumor-associated immune cell effector gene expression levels were associated with lower ATP1A3 expression. In addition, immunotherapy prediction pathway activity and a majority of the anti-cancer immune cell process activity levels were also showed to be correlated with lower ATP1A3 gene expression. Further, nine prognostic factors were identified by prognostic analysis, and a GBM prognostic model (risk score) was established. We applied the model to the TCGA GBM training set sample and the GSE4412 validation set sample and found that patients in the high risk score subgroup had significantly shorter survival time, demonstrating the prognostic value and prognostic efficacy of the risk score. Furthermore, ATP1A3 overexpression has also been found to sensitize cancer cells to anti-PD-1 therapy. In conclusion, we showed that ATP1A3 is a highly promising treatment target in GBM and the risk score is an independent prognostic factor for cancer and can be used to help guide the prediction of survival time in patients with GBM.

Is There a Role of Vitamin D in Alzheimer's Disease?

Alzheimer's disease (AD) represents the most prevalent type of neurodegenerative dementia and the sixth leading cause of death worldwide. The so-called "non-calcemic actions" of vitamin D have been increasingly described, and its insufficiency has already been linked to the onset and progression of the main neurological diseases, including AD. Immune-mediated Aβ plaque's phagocytosis and clearance, immune response, oxidative stress, and mitochondrial function are all influenced by vitamin D, and these functions are considered relevant in AD pathogenesis. However, it has been shown that the genomic vitamin D signaling pathway is already impaired in the AD brain, making things more complicated. In this paper, we aim to summarise the role of vitamin D in AD and review the results of the supplementation trials in AD patients.

Sporadic Creutzfeldt-Jakob disease in adults over 80years: a 10-year review of United Kingdom surveillance.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive neurodegenerative disease with public health implications. Mean age of onset is 68years. Age-specific incidence declines after 80years. This may arise from under-ascertainment or other biological features of the disease. Accurate characterisation of late-onset sCJD is important for early diagnosis, avoiding unnecessary investigations and improving ascertainment for public health purposes. To phenotype the clinical features and investigation profile of sCJD in adults >80years. We analysed all probable and definite sCJD cases identified by the UK National CJD Research & Surveillance Unit over a 10-year period (2011-2021). Individuals were grouped by age of onset. Clinical features and investigation profiles were compared. 10.3% (123/1196) had an age of onset over 80. Median survival was shorter (3.2 vs 4.3months; P < 0.001). Pyramidal signs (48.3% vs 34.2%; P = 0.008) and akinetic mutism (55.1% vs 33.2%; P < 0.001) were more frequent. Psychiatric symptoms (26.3% vs 39.6%; P = 0.01) and cerebellar signs (65.4% vs 78.6%, P = 0.007) were less frequent. Cognitive impairment and myoclonus were highly prevalent regardless of age. Between age groups, the diagnostic sensitivity of cerebrospinal fluid real-time quaking-induced conversion (CSF RT-QuIC) (92.9% vs 91.9%, P = 0.74) was comparable, electroencephalography was superior (41.5% vs 25.4%; P = 0.006) and MRI was inferior (67.8% vs 91.4%; P < 0.001). Late-onset sCJD has distinct clinical features, shorter survival and a different profile of investigation sensitivity. CSF RT-QuIC, MRI brain and specialist CJD review is recommended in older adults with a rapidly progressive neurological disorder. Autopsy is valuable when the cause remains elusive.

Probing Protein Structural Changes in Alzheimer's Disease via Quantitative Cross-linking Mass Spectrometry.

Alzheimer's disease (AD) is a progressive neurological disorder featuring abnormal protein aggregation in the brain, including the pathological hallmarks of amyloid plaques and hyperphosphorylated tau. Despite extensive research efforts, understanding the molecular intricacies driving AD development remains a formidable challenge. This study focuses on identifying key protein conformational changes associated with the progression of AD. To achieve this, we employed quantitative cross-linking mass spectrometry (XL-MS) to elucidate conformational changes in the protein networks in cerebrospinal fluid (CSF). By using isotopically labeled cross-linkers BS3d0 and BS3d4, we reveal a dynamic shift in protein interaction networks during AD progression. Our comprehensive analysis highlights distinct alterations in protein-protein interactions within mild cognitive impairment (MCI) states. This study accentuates the potential of cross-linked peptides as indicators of AD-related conformational changes, including previously unreported site-specific binding between α-1-antitrypsin (A1AT) and complement component 3 (CO3). Furthermore, this work enables detailed structural characterization of apolipoprotein E (ApoE) and reveals modifications within its helical domains, suggesting their involvement in MCI pathogenesis. The quantitative approach provides insights into site-specific interactions and changes in the abundance of cross-linked peptides, offering an improved understanding of the intricate protein-protein interactions underlying AD progression. These findings lay a foundation for the development of potential diagnostic or therapeutic strategies aimed at mitigating the negative impact of AD.

The efficacy of NIV in patients affected by Rett syndrome with hypoventilation

IntroductionRett syndrome is a progressive neurological disorder associated to several comorbidities that contribute significantly to impair lung function. Respiratory morbidity represents a major cause of death in this population. Little is known about the benefit of non-invasive ventilation. Methodswe retrospectively enrolled patients with Rett syndrome who underwent a pneumological evaluation combined with a cardio-respiratory polygraphy and/or a pulse oximetry and capnography from 2012 to 2022. Resultsmedical records of eleven patients with Rett syndrome, mean age 13 ± 6 years, were evaluated. Most patients presented both with epilepsy and scoliosis. Five patients showed a pathological sleep study and/or impaired night gas exchange: mean obstructive apnea/hypopneas index was 4 ± 3 events/h; mean and minimal SpO2 were respectively 93 ± 2 % and 83± 6 %, while mean and maximal PtcCO2 were, respectively, 51 ± 5 mmHg and 55 ± 8 mmHg; mean oxygen desaturation index was 13 ± 11 events/h. These patients started non-invasive ventilation with clinical benefit and improved gas exchange mostly in terms of PtCO2 (mean PtCO2 51 ± 5 mmHg before and 46 ± 6 mmHg after non-invasive ventilation). Conclusionnon-invasive ventilation is a suitable option for patients with Rett syndrome.

Sandhoff's Disease: A Case Report

Sandhoff disease is a rare inherited disorder within the sphingolipidosis family, characterized by the accumulation of lipids in the nervous system due to a deficiency in hexosaminidase types A and B enzymes. This condition leads to progressive neurological disorders and eventual blindness, often resulting in fatality before the age of 4. We present the case of an infant who was admitted for psychomotor regression and generalized hypotonia, with the diagnosis of Sandhoff disease being supported by ophthalmological examination findings. Confirmation of the diagnosis was achieved through exome sequencing.

Feature Importance Analysis and Machine Learning for Alzheimer's Disease Early Detection: Feature Fusion of the Hippocampus, Entorhinal Cortex, and Standardized Uptake Value Ratio.

Alzheimer's disease (AD) is a progressive neurological disorder characterized by mild memory loss and ranks as a leading cause of mortality in the USA, accounting for approximately 120,000 deaths per year. It is also the primary form of dementia. Early detection is critical for timely intervention as the neurodegenerative process often starts 15-20 years before cognitive symptoms manifest. This study focuses on determining feature importance in AD classification using fused texture features from 3D magnetic resonance imaging hippocampal and entorhinal cortex and standardized uptake value ratio (SUVR) derived from positron emission tomography (PET) images. To achieve this objective, we employed four distinct classifiers (Linear Support Vector Classification, Linear Discriminant Analysis, Logistic Regression, and Logistic Regression Classifier with Stochastic Gradient Descent Learning). These classifiers were used to derive both average and top-ranked importance scores for each feature based on their outputs. Our framework is designed to distinguish between two classes, AD-negative (or mild cognitive impairment stable [MCIs]) and AD-positive (or MCI conversion [MCIc]), using a probabilistic neural network classifier and the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The findings from the feature importance highlight the crucial role of the GLCM texture features extracted from the hippocampus and entorhinal cortex, demonstrating their superior performance compared to the volume and SUVR. GLCM texture AD classification achieved approximately 90% sensitivity in identifying MCIc cases while maintaining low false positives (below 30%) when fused with other features. Moreover, the receiver operating characteristic curves validate the GLCMs' superior performance in distinguishing between MCIs and MCIc. Additionally, fusing different types of features improved classification performance compared to relying solely on any single feature category. Our study emphasizes the pivotal role of GLCM texture features in early Alzheimer's detection.

Transferrin-conjugated magnetic nanoparticles for the isolation of brain-derived blood exosomal MicroRNAs: A novel approach for Parkinson's disease diagnosis

BackgroundBrain-derived exosomes circulate in the bloodstream and other bodily fluids, serving as potential indicators of neurological disease progression. These exosomes present a promising avenue for the early and precise diagnosis of neurodegenerative conditions. Notably, miRNAs found in plasma extracellular vesicles (EVs) offer distinct diagnostic benefits due to their stability, abundance, and resistance to breakdown. ResultsIn this study, we introduce a method using transferrin conjugated magnetic nanoparticles (TMNs) to isolate these exosomes from the plasma of patients with neurological disorders. This TMNs technique is both quick (<35 min) and cost-effective, requiring no high-priced ingredients or elaborate equipment for EV extraction. Our method successfully isolated EVs from 33 human plasma samples, including those from patients with Parkinson's disease (PD), Multiple Sclerosis (MS), and Dementia. Using quantitative polymerase chain reaction (PCR) analysis, we evaluated the potential of 8 exosomal miRNA profiles as biomarker candidates. Six exosomal miRNA biomarkers (miR-195-5p, miR-495-3p, miR-23b-3P, miR-30c-2-3p, miR-323a-3p, and miR-27a-3p) were consistently linked with all stages of PD. SignificanceThe TMNs method provides a practical, cost-efficient way to isolate EVs from biological samples, paving the way for non-invasive neurological diagnoses. Furthermore, the identified miRNA biomarkers in these exosomes may emerge as innovative tools for precise diagnosis in neurological disorders including PD.

Gut Microbiome Changes in Patients With Idiopathic Normal Pressure Hydrocephalus.

The gut microbiome is a complex system within the human gastrointestinal tract. The bacteria play a significant role in human health, and some can promote inflammation and pathologic processes through chemical interactions or metabolites. Gut microbiome dysbiosis has been linked to some neurological and other diseases. Here we aimed to examine microbiome differences between patients with a progressive neurological disorder, idiopathic normal pressure hydrocephalus (iNPH), compared with healthy controls (CO). We recruited 37 neurologically healthy CO and 10 patients with shunted iNPH. We evaluated these participants' cognition using the CERAD-NB test battery and CDR test, and collected a variety of information, including about dietary habits and health. We also collected fecal samples, which were subjected to 16S amplicon sequencing to analyze differences in gut microbiome composition. We found that the iNPH group exhibited significantly different abundances of 10 bacterial genera compared with the CO group. The Escherichia/Shigella and Anaeromassilibacillus genera were most remarkably increased. Other increased genera were Butyrivibrio, Duncaniella, and an unidentified genus. The decreased genera were Agathobaculum, Paramuribaculum, Catenibacterium, and 2 unidentified genera. Here we report the first identified microbiome differences in iNPH patients compared with healthy controls.

SCA 15 presenting with parkinsonism–dystonia, tremor, and psychosis in an Indian woman

Abstract Spinocerebellar ataxias (SCAs) represent a diverse group of hereditary and progressive neurological disorders characterized by their onset in adulthood and commonly exhibit autosomal dominant inheritance. These disorders typically involve multiple brain regions, including the cerebellum, spinal cord, basal ganglia, brainstem, and cortical areas, leading to varied and heterogeneous clinical presentations. In particular, SCA 15 is recognized as an adult-onset, slowly progressive cerebellar syndrome, often accompanied by various other neurological manifestations. In this report, we present a novel clinical phenotype of parkinsonism–dystonia syndrome co-occurring with cerebellar features in a genetically confirmed case of SCA 15.

Aging brain: exploring the interplay between bone marrow aging, immunosenescence, and neuroinflammation.

Aging is a complex process characterized by a myriad of physiological changes, including alterations in the immune system termed immunosenescence. It exerts profound effects on both the bone marrow and the central nervous system, with significant implications for immunosenescence in neurological contexts. Our mini-review explores the complex relationship between bone marrow aging and its impact on immunosenescence, specifically within the context of neurological diseases. The bone marrow serves as a crucial hub for hematopoiesis and immune cell production, yet with age, it undergoes significant alterations, including alterations in hematopoietic stem cell function, niche composition, and inflammatory signaling. These age-related shifts in the bone marrow microenvironment contribute to dysregulation of immune cell homeostasis and function, impacting neuroinflammatory processes and neuronal health. In our review, we aim to explore the complex cellular and molecular mechanisms that link bone marrow aging to immunosenescence, inflammaging, and neuroinflammation, with a specific focus on their relevance to the pathophysiology of age-related neurological disorders. By exploring this interplay, we strive to provide a comprehensive understanding of how bone marrow aging impacts immune function and contributes to the progression of neurological diseases in aging individuals. Ultimately, this knowledge can hold substantial promise for the development of innovative therapeutic interventions aimed at preserving immune function and mitigating the progression of neurological disorders in the elderly population.

Immunological Implications in Diabetes: A Review on Various Diseases and Conditions

Abstract:: Diabetes Mellitus (DM) is a long-term metabolic condition that has significant social, health, and economic consequences. There are various forms of diabetes mellitus, but the two most common varieties are type I and type II. Insulin-dependent diabetes (IDDM) is one of the most wellknown autoimmune illnesses that cause insulin insufficiency and hyperglycemia by either damaging or destroying Langerhans' beta cells. Available scientific data evidenced the greatest genetic contribution of Human Leukocyte Antigen class II in the IDDM. Hyperglycemia and individual components of the insulin resistance (metabolic) syndrome put people with type II diabetes at increased risk for microvascular consequences (retinopathy, nephropathy, and neuropathy) as well as macrovascular issues (cardiovascular comorbidities). A number of pathophysiological abnormalities, including obesity, poor diet, and physical inactivity, as well as genetic variables, are involved in the disturbed glucose homeostasis associated with type II diabetes. Diseases like lipid abnormalities contribute to the progression of diabetes, whereas obesity and its related medical disorders (such as hypertension, diabetes, insulin resistance, and sleep apnea syndrome) are eventually linked to an elevated cardiovascular risk. Diabetes raises the incidence, intensity, and duration of peri-densities in people with diabetes compared to healthy persons, making it a risk factor for periodontal disease. Diabetes conditions in patients concurrently also increase the progression or risk of other diseases, i.e., cardiovascular- related diseases (hypertension, oxidative stress, hyperlipidemia), nervous system-related diseases, and COVID-19, by increasing the overall infection rate. There is widespread evidence that correlates the direct connection between diabetes and other diseases, including immunity disorders, CVS disorders, etc. This review provides a correlation between diabetes and another disease with an overall impact on the progression of cardiovascular diseases, neurological diseases, COVID-19, and periodontal diseases. This current review focuses on the collation of some plants that show antidiabetic activity, including plant part, family, chemical constituent, mechanism of action, and chemical used for extraction. Studies on the role, causes, clinical management, prevention, and treatment of diabetes heavily rely on epidemiological evidence. This review also explains different factors responsible for diabetes, like genetic factors, environmental factors, and viral infections.

V-set and immunoglobulin domain containing 4 inhibits oxidative stress, mitochondrial dysfunction, and inflammation to attenuate Parkinson's disease progression by activating the JAK2/STAT3 pathway

ObjectiveV-set and immunoglobulin domain containing 4 (VSIG4) inhibits neurological dysfunction, microglial M1 polarization, and inflammation to participate in the progression of neurological disorders, but evidence regarding Parkinson's disease (PD) is scarce. The present study intended to investigate the engagement of VSIG4 in PD progression, and the potential mechanism. MethodsBV-2 cells were treated with 1-Methyl-4-phenylpyridinium (MPP+) to establish PD model. MPP+ treated BV-2 cells were infected with VSIG4 overexpression adenovirus-associated virus (AAV) (oeVSIG4) and negative control AAV (oeNC), and AZD1480 (JAK2 inhibitor) was added to these cells. ResultsMPP+ reduced VSIG4 mRNA (P < 0.05) and protein (P < 0.05) in BV-2 cells. Interestingly, VSIG4 reduced malondialdehyde (P < 0.01), reactive oxygen species (P < 0.01), NOD-like receptor family pyrin domain containing 3 (P < 0.05), cleaved-caspase1 (P < 0.05), tumor necrosis factor-α (P < 0.05), and interleukin-1β (P < 0.05), but increased glutathione (P < 0.05), mitochondrial membrane potential (P < 0.05), phosphorylation (p)-JAK2 (P < 0.05), and p-STAT3 (P < 0.01) in MPP+ treated BV-2 cells, which indicated that VSIG4 inhibited oxidative stress, mitochondrial dysfunction, and inflammation, as well as activated the JAK2/STAT3 pathway in PD model. Moreover, AZD1480 inhibited the JAK2/STAT3 pathway and aggravated oxidative stress, mitochondrial dysfunction, and inflammation in PD model (all P < 0.05). Importantly, AZD1480 attenuated the influence of VSIG4 on oxidative stress, mitochondrial dysfunction, inflammation, and the JAK2/STAT3 pathway in PD model (all P < 0.05). ConclusionVSIG4 suppresses oxidative stress, mitochondrial dysfunction, and inflammation by activating the JAK2/STAT3 pathway, which may be helpful in attenuating PD progression.

Dynamic microglia alterations associate with hippocampal network impairments: A turning point in amyloid pathology progression

Alzheimer's disease is a progressive neurological disorder causing memory loss and cognitive decline. The underlying causes of cognitive deterioration and neurodegeneration remain unclear, leading to a lack of effective strategies to prevent dementia. Recent evidence highlights the role of neuroinflammation, particularly involving microglia, in Alzheimer's disease onset and progression. Characterizing the initial phase of Alzheimer's disease can lead to the discovery of new biomarkers and therapeutic targets, facilitating timely interventions for effective treatments.We used the AppNL-G-F knock-in mouse model, which resembles the amyloid pathology and neuroinflammatory characteristics of Alzheimer’s disease, to investigate the transition from a pre-plaque to an early plaque stage with a combined functional and molecular approach.Our experiments show a progressive decrease in the power of cognition-relevant hippocampal gamma oscillations during the early stage of amyloid pathology, together with a modification of fast-spiking interneuron intrinsic properties and postsynaptic input. Consistently, transcriptomic analyses revealed that these effects are accompanied by changes in synaptic function-associated pathways. Concurrently, homeostasis- and inflammatory-related microglia signature genes were downregulated. Moreover, we found a decrease in Iba1-positive microglia in the hippocampus that correlates with plaque aggregation and neuronal dysfunction. Collectively, these findings support the hypothesis that microglia play a protective role during the early stages of amyloid pathology by preventing plaque aggregation, supporting neuronal homeostasis, and overall preserving the oscillatory network’s functionality.These results suggest that the early alteration of microglia dynamics could be a pivotal event in the progression of Alzheimer's disease, potentially triggering plaque deposition, impairment of fast-spiking interneurons, and the breakdown of the oscillatory circuitry in the hippocampus.

A rare complication of measles infection presented with subacute sclerosing panencephalitis: Report of two cases in India

Rationale: Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder caused by persistent measles virus infection. SSPE predominantly affects children and adolescents. The symptoms usually develop 6-15 years after measles infection and ultimately leading to death in many cases. Patient concerns: Patient 1 presented with cognitive decline and myoclonus and the Patient 2 presented with diminution of vision with myoclonic jerks. Diagnosis: Based on the clinical features with a characteristic electroencephalogram pattern and the presence of a high titer of anti-measles IgG in serum and cerebrospinal fluid, these patients were diagnosed as SSPE. Interventions: Antiepileptics were started for controlling myoclonus along with supportive treatment. Outcomes: Both patients were discharged on antiepileptics and supportive care. Lessons: Whenever there are unusual clinical manifestations with unknown vaccination status, SSPE can be suspected and the cerebrospinal fluid should be examined for anti-measles antibodies. Our case study also highlights the importance of universal coverage of measles vaccination. To reduce the incidence of measles and associated deaths, it is important to maintain a high level of immunization coverage for the measles vaccine and to strengthen all the integral components of the national immunization program.

Exploring the Potential of Deep Learning in the Classification and Early Detection of Parkinson's Disease

INTRODUCTION: Parkinson's Disease (PD) is a progressive neurological disorder affecting a significant portion of the global population, leading to profound impacts on daily life and imposing substantial burdens on healthcare systems. Early identification and precise classification are crucial for effectively managing this disease. This research investigates the potential of deep learning techniques in facilitating early recognition and accurate classification of PD.&#x0D; OBJECTIVES: The primary objective of this study is to leverage advanced deep learning techniques for the early detection and precise classification of Parkinson's Disease. By utilizing a rich dataset comprising speech signal features extracted from 3000 PD patients, including Time Frequency Features, Mel Frequency Cepstral Coefficients (MFCCs), Wavelet Transform based Features, Vocal Fold Features, and TWQT features, this research aims to evaluate the performance of various deep learning models in PD classification.&#x0D; METHODS: The dataset containing diverse speech signal features from PD patients' recordings serves as the foundation for training and evaluating five different deep learning models: ResNet50, VGG16, Inception v2, AlexNet, and VGG19. Each model undergoes training and assessment to determine its capability in accurately classifying PD patients. Performance metrics such as accuracy are employed to evaluate the models' effectiveness.&#x0D; RESULTS: The results demonstrate promising potential, with overall accuracies ranging from 89% to 95% across the different deep learning models. Notably, AlexNet emerges as the top-performing model, achieving an accuracy of 95% and demonstrating balanced performance in accurately identifying both true and false PD cases.&#x0D; CONCLUSION: This research highlights the significant potential of deep learning in facilitating the early detection and classification of Parkinson's Disease. Leveraging speech signal features offers a non-invasive and cost-effective approach to PD assessment. The findings contribute to the growing body of evidence supporting the integration of artificial intelligence in healthcare, particularly in the realm of neurodegenerative disorders. Further exploration into the application of deep learning in this domain holds promise for advancing PD diagnosis and management.

Bridging the gap: R-loop mediated genomic instability and its implications in neurological diseases.

R-loops, intricate three-stranded structures formed by RNA-DNA hybrids and an exposed non-template DNA strand, are fundamental to various biological phenomena. They carry out essential and contrasting functions within cellular mechanisms, underlining their critical role in maintaining cellular homeostasis. The specific cellular context that dictates R-loop formation determines their function, particularly emphasizing the necessity for their meticulous genomic regulation. Notably, the aberrant formation or misregulation of R-loops is implicated in numerous neurological disorders. This review focuses on the complex interactions between R-loops and double-strand DNA breaks, exploring how R-loop dysregulation potentially contributes to the pathogenesis of various brain disorders, which could provide novel insights into the molecular mechanisms underpinning neurological disease progression and identify potential therapeutic targets by highlighting these aspects.

Elimination of virus-like particles reduces protein aggregation and extends replicative lifespan in Saccharomyces cerevisiae

A major consequence of aging and stress, in yeast to humans, is an increased accumulation of protein aggregates at distinct sites within the cells. Using genetic screens, immunoelectron microscopy, and three-dimensional modeling in our efforts to elucidate the importance of aggregate annexation, we found that most aggregates in yeast accumulate near the surface of mitochondria. Further, we show that virus-like particles (VLPs), which are part of the retrotransposition cycle of Ty elements, are markedly enriched in these sites of protein aggregation. RNA interference-mediated silencing of Ty expression perturbed aggregate sequestration to mitochondria, reduced overall protein aggregation, mitigated toxicity of a Huntington's disease model, and expanded the replicative lifespan of yeast in a partially Hsp104-dependent manner. The results are in line with recent data demonstrating that VLPs might act as aging factors in mammals, including humans, and extend these findings by linking VLPs to a toxic accumulation of protein aggregates and raising the possibility that they might negatively influence neurological disease progression.