Neuroprotective Effects of VEGF-B in a Murine Model of Aggressive Neuronal Loss with Childhood Onset.

In recent decades, the scientific community has faced a major challenge in the search for new therapies that can slow down or alleviate the process of neuronal death that accompanies neurodegenerative diseases. This study aimed to identify an effective therapy using neurotrophic factors to delay the rapid and aggressive cerebellar degeneration experienced by the Purkinje Cell Degeneration (PCD) mouse, a model of childhood-onset neurodegeneration with cerebellar atrophy (CONDCA). Initially, we analyzed the changes in the expression of several neurotrophic factors related to the degenerative process itself, identifying changes in insulin-like growth factor 1 (IGF-1) and Vascular Endothelial Growth Factor B (VEGF-B) in the affected animals.

HERV-W Env Induces Neuron Pyroptosis via the NLRP3-CASP1-GSDMD Pathway in Recent-Onset Schizophrenia.

HERVs (Human endogenous retroviruses) are remnants of ancient exogenous retroviruses that have integrated into the human genome, particularly in germ-line cells. Among these, the envelope protein gene (Human endogenous retroviruses W family envelope protein), located on chromosome 7 and primarily expressed in the human placenta, has been closely linked to various neuropsychiatric disorders, including schizophrenia, as well as autoimmune diseases and cancer. Recent studies have highlighted the abnormal expression of cytokines as a key factor in the pathophysiology of schizophrenia.

Evidence Suggesting That Alzheimer's Disease May Be a Transmissible Disorder.

Alzheimer's disease (AD) is characterised by progressive neurodegeneration with the formation of amyloid beta (Aβ) plaques and neurofibrillary tau tangles in the brain parenchyma. The causes of AD have been attributed to a combination of age-related changes within the brain as well as genetic, environmental and lifestyle factors. However, a recent study by Banerjee et al.

Degenerative Disease Diagnosis and Analysis Based on Tissue Specificity of DNA Methylation.

The tissue specificity of DNA methylation refers to the significant differences in DNA methylation patterns in different tissues. This specificity regulates gene expression, thereby supporting the specific functions of each tissue and the maintenance of normal physiological activities. Abnormal tissue-specific patterns of DNA methylation are closely related to age-related diseases.

Oxidative Stress and Risk of Dementia in Older Patients with Depression: A Longitudinal Cohort Study Using Plasma Biomarkers.

: While depression is associated with an increased risk of Alzheimer's dementia (AD), traditional AD-related biomarkers, such as amyloid-beta, have shown limited predictive value for late-life depression. Oxidative stress has emerged as a potential indicator given its shared role in both depression and dementia. This study investigated the longitudinal relationship between oxidative stress biomarkers and risk of dementia in patients with depression.

Functional and Cognitive Impairment in Patients with Relapsing-Remitting Multiple Sclerosis: Cognitive Tests and Plasma Neurofilament Light Chain Levels.

Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system. The disease can manifest and progress with both physical and cognitive symptoms, affecting the patient's daily activities. The aim of our study was to investigate the correlation between functional status, cognitive functions, and neurofilament light chain levels in plasma in MS patients.

Atypical Leber Hereditary Optic Neuropathy (LHON) Associated with a Novel MT-CYB:m.15309T>C(Ile188Thr) Variant.

The study presents a detailed examination and follow-up of a Slovenian patient with an Leber Hereditary Optic Neuropathy (LHON)-like phenotype and bilateral optic neuropathy in whom genetic analysis identified a novel variant :m.15309T>C (Ile188Thr). We provide detailed analysis of the clinical examinations of a male patient with bilateral optic neuropathy from the acute stage to 8 years of follow-up.

Proteostasis Decline and Redox Imbalance in Age-Related Diseases: The Therapeutic Potential of NRF2.

Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular homeostasis, overseeing the expression of a wide array of genes involved in cytoprotective processes such as antioxidant and proteostasis control, mitochondrial function, inflammation, and the metabolism of lipids and glucose. The accumulation of misfolded proteins triggers the release, stabilization, and nuclear translocation of NRF2, which in turn enhances the expression of critical components of both the proteasomal and lysosomal degradation pathways. This process facilitates the clearance of toxic protein aggregates, thereby actively maintaining cellular proteostasis.

Saponins Effect on Human Insulin Amyloid Aggregation.

The misfolding and amyloid aggregation of proteins have been attracting scientific interest for a few decades, due to their link with several diseases, particularly neurodegenerative diseases. Proteins can assemble and result in insoluble aggregates that, together with intermediate oligomeric species, modify the extracellular environment. Many efforts have been and are devoted to the search for cosolvents and cosolutes able to interfere with amyloid aggregation.

Insights into the Allosteric Regulation of Human Hsp90 Revealed by NMR Spectroscopy.

Human heat shock protein 90 (Hsp90) is one of the most important chaperones that play a role in the late stages of protein folding. Errors in the process of the chaperone cycle can lead to diseases such as cancer and neurodegenerative diseases. Therefore, the activity of Hsp90 must be carefully regulated.

The Role of Air Pollution and Olfactory Dysfunction in Alzheimer's Disease Pathogenesis.

The escalating issue of air pollution contributes to an alarming number of premature fatalities each year, thereby posing a significant threat to global health. The focus of recent research has shifted towards understanding its potential association with neurodegenerative diseases, specifically Alzheimer's disease (AD). AD is recognised for its characteristic deposition of toxic proteins within the brain, leading to a steady deterioration of cognitive capabilities, memory failure, and, ultimately, death.

Novel Role of Pin1-Cis P-Tau-ApoE Axis in the Pathogenesis of Preeclampsia and Its Connection with Dementia.

Preeclampsia (preE) is a severe multisystem hypertensive syndrome of pregnancy associated with ischemia/hypoxia, angiogenic imbalance, apolipoprotein E (ApoE)-mediated dyslipidemia, placental insufficiency, and inflammation at the maternal-fetal interface. Our recent data further suggest that preE is associated with impaired autophagy, vascular dysfunction, and proteinopathy/tauopathy disorder, similar to neurodegenerative diseases such as Alzheimer's disease (AD), including the presence of the cis stereo-isoform of phosphorylated tau (cis P-tau), amyloid-β, and transthyretin in the placenta and circulation. This review provides an overview of the factors that may lead to the induction and accumulation of cis P-tau-like proteins by focusing on the inactivation of peptidyl-prolyl cis-trans isomerase (Pin1) that catalyzes the cis to trans isomerization of P-tau.

Targeting Mitochondrial Dysfunction in Cerebral Ischemia: Advances in Pharmacological Interventions.

The study of mitochondrial dysfunction has become increasingly pivotal in elucidating the pathophysiology of various cerebral pathologies, particularly neurodegenerative disorders. Mitochondria are essential for cellular energy metabolism, regulation of reactive oxygen species (ROS), calcium homeostasis, and the execution of apoptotic processes. Disruptions in mitochondrial function, driven by factors such as oxidative stress, excitotoxicity, and altered ion balance, lead to neuronal death and contribute to cognitive impairments in several brain diseases.

Mutations of the Electron Transport Chain Affect Lifespan and ROS Levels in .

Mutations in highly conserved genes encoding components of the electron transport chain (ETC) provide valuable insights into the mechanisms of oxidative stress and mitochondrial ROS (mtROS) in a wide range of diseases, including cancer, neurodegenerative disorders, and aging. This review explores the structure and function of the ETC in the context of its role in mtROS generation and regulation, emphasizing its dual roles in cellular damage and signaling. Using as a model organism, we discuss how ETC mutations manifest as developmental abnormalities, lifespan alterations, and changes in mtROS levels.

GENI as an AMPK Activator Binds α and γ Subunits and Improves the Memory Dysfunction of Alzheimer's Disease Mouse Models via Autophagy and Neuroprotection.

Geniposidic 4-isoamyl ester (GENI) with anti-aging effects is a new iridoid glycoside derivative from Ellis found in our previous study. In this study, to indicate whether this compound has anti-Alzheimer's disease (AD) effect, the galactose-induced AD mice and naturally aging mice with AD were used to do drug efficacy evaluation. Furthermore, the Western blot, small interfering RNA (siRNA), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CESTA), liquid chromatography-tandem mass spectrometry (LC/MS-MS), adenosine 5'-monophosphate-activated protein kinase (AMPK) mutants and surface plasmon resonance (SPR) analysis were utilized to clarify the mechanism of action and identify target protein of this molecule.

Antioxidant, Anti-α-Glucosidase, Anti-Tyrosinase, and Anti-Acetylcholinesterase Components from Stem of with Molecular Docking Study.

is a creeping evergreen shrub endemic to Taiwan. In traditional medicine, Rhamnaceae plants are used as herbal remedies for conditions such as itching, difficulty urinating, and constipation. This study explores the inhibitory effects of various solvent extracts and bioactive components of on α-glucosidase, tyrosinase, acetylcholinesterase (AChE), and antioxidant activity.

Assessment of Peripheral Neuropathy Using Current Perception Threshold Measurement in Patients with Spinocerebellar Ataxia Type 3.

Peripheral neuropathy (PN) identified as a significant contributor to disability in Spinocerebellar ataxia type 3 (SCA3) patients. This study seeks to assess the utility of current perception threshold (CPT) measurements in evaluating PN in individuals with SCA3 and aims to identify factors influencing CPT values in SCA3 and ascertain whether these values correlate with the severity of ataxia. Ninety-four patients diagnosed with SCA3 and 44 healthy controls were recruited for this investigation.

Identifying time patterns in Huntington's disease trajectories using dynamic time warping-based clustering on multi-modal data.

One of the principal goals of Precision Medicine is to stratify patients by accounting for individual variability. However, extracting meaningful information from Real-World Data, such as Electronic Health Records, still remains challenging due to methodological and computational issues. A Dynamic Time Warping-based unsupervised-clustering methodology is presented in this paper for the clustering of patient trajectories of multi-modal health data on the basis of shared temporal characteristics.

Multiomics approach identifies dysregulated lipidomic and proteomic networks in Parkinson's disease patients mutated in TMEM175.

Parkinson's disease (PD) represents one of the most frequent neurodegenerative disorders for which clinically useful biomarkers remain to be identified and validated. Here, we adopted an untargeted omics approach to disclose lipidomic, metabolomic and proteomic alterations in plasma and in dermal fibroblasts of PD patients carrying mutations in TMEM175 gene. We revealed a wide dysregulation of lysosome, autophagy, and mitochondrial pathways in these patients, supporting a role of this channel in regulating these cellular processes.

Free radicals and their impact on health and antioxidant defenses: a review.

Free radicals, characterized by the presence of unpaired electrons, are highly reactive species that play a significant role in human health. These molecules can be generated through various endogenous processes, such as mitochondrial respiration and immune cell activation, as well as exogenous sources, including radiation, pollution, and smoking. While free radicals are essential for certain physiological processes, such as cell signaling and immune defense, their overproduction can disrupt the delicate balance between oxidants and antioxidants, leading to oxidative stress.

Chromatin accessibility provides a window into the genetic etiology of human brain disease.

Neuropsychiatric and neurodegenerative diseases have a significant genetic component. Risk variants often affect the noncoding genome, altering cis-regulatory elements (CREs) and chromatin structure, ultimately impacting gene expression. Chromatin accessibility profiling methods, especially assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), have been used to pinpoint disease-associated SNPs and link them to affected genes and cell types in the brain.

Stem-leaf saponins of Panax notoginseng attenuate experimental Parkinson's disease progression in mice by inhibiting microglia-mediated neuroinflammation via P2Y2R/PI3K/AKT/NFκB signaling pathway.

Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice.

Ecopsychosocial strategies for the self-exploration of professional family caregivers to manage the behavioural and psychological symptoms of Alzheimer patients in Iran: a qualitative study.

Objective: The aim of the present study was to explore the experiences and viewpoints of professional family caregivers in the management of behavioural and psychological symptoms of dementia (BPSDs) to identify the ecopsychosocial strategies applied by them.

Design: Qualitative study.

Setting: Kerman, Iran.

Longitudinally persisting KCNA2-autoantibodies in mild amnestic dementia with Alzheimer´s pathology - report and literature review.

Background: Neural autoantibodies are being increasingly detected in conjunction with neurodegenerative dementias such as Alzheimer's disease dementia (AD), yet their significance is not well clarified. In this case report, we report the previously unreported long-lasting persistence of potassium voltage-gated channel subfamily A member 2 (KCNA2) antibodies in biomarker-supported AD.

Methods: We report on a 77-year-old, male patient evaluated in our outpatient memory clinic of the Department of Psychiatry and Psychotherapy, University Medical Center Göttingen.

Roles of NLRC4 inflammasome in neurological disorders: Mechanisms, implications, and therapeutic potential.

The nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 4 (NLRC4) inflammasome, a vital component of the innate immune system, is known for defending against bacterial infections. However, recent insights have revealed its significant impact on neurological disorders. This comprehensive review discussed the mechanisms underlying the activation and regulation of the NLRC4 inflammasome, highlighting the complexity of its response to cellular stress and damage signals.