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.

THE RATIO OF EXCITATORY AND INHIBITORY SYNAPTIC PROCESSES IN NEURONS OF THE ЕNTORHINAL CORTEX OF THE BRAIN, ACTIVATED BY BASOLATERAL AMYGDALA ON THE MODEL OF PARKINSON'S DISEASE, UNDER CONDITIONS OF PROTECTION BY HYDROCORTISONE.

Parkinson disease (PD) is a common neurodegenerative condition. It affects the central nervous system, and it impairs cognitive processes, motor skills and other functions. The aim of this study was to determine the synaptic processes in medial Entorhinal cortex (mENT) under High frequency stimulation of Basolateral Amygdala on the model of Parkinson's disease under the influence of Hydrocortisone.

Behavioral Profiling in Zebrafish Identifies Insecticide-Related Compounds.

Pesticides, including insecticides, are indispensable for large-scale agriculture. Modulating chloride ion channels has proven highly successful as a mode of action (MoA) for insect management. Identifying new ligands for these channels affords opportunities for the potential development of new insecticide products.

NK cell exhaustion in Wilson's disease revealed by single-cell RNA sequencing predicts the prognosis of cholecystitis.

Metabolic abnormalities associated with liver disease have a significant impact on the risk and prognosis of cholecystitis. However, the underlying mechanism remains to be elucidated. Here, we investigated this issue using Wilson's disease (WD) as a model, which is a genetic disorder characterized by impaired mitochondrial function and copper metabolism.

Weight trajectories in aging humanized APOE mice with translational validity to human Alzheimer's risk population: A retrospective analysis.

Translational validity of mouse models of Alzheimer's disease (AD) is variable. Because change in weight is a well-documented precursor of AD, we investigated whether diversity of human AD risk weight phenotypes was evident in a longitudinally characterized cohort of 1,196 female and male humanized APOE (hAPOE) mice, monitored up to 28 months of age which is equivalent to 81 human years. Autoregressive Hidden Markov Model (AHMM) incorporating age, sex, and APOE genotype was employed to identify emergent weight trajectories and phenotypes.

Assessment of temporospatial and kinematic gait parameters using human pose estimation in patients with Parkinson's disease: A comparison between near-frontal and lateral views.

Gait disturbance is one of the most common symptoms in patients with Parkinson's disease (PD) that is closely associated with poor clinical outcomes. Recently, video-based human pose estimation (HPE) technology has attracted attention as a cheaper and simpler method for performing gait analysis than marker-based 3D motion capture systems. However, it remains unclear whether video-based HPE is a feasible method for measuring temporospatial and kinematic gait parameters in patients with PD and how this function varies with camera position.

Lipid-induced condensate formation from the Alzheimer's Aβ peptide triggers amyloid aggregation.

The onset and development of Alzheimer's disease is linked to the accumulation of pathological aggregates formed from the normally monomeric amyloid-β peptide within the central nervous system. These Aβ aggregates are increasingly successfully targeted with clinical therapies at later stages of the disease, but the fundamental molecular steps in early stage disease that trigger the initial nucleation event leading to the conversion of monomeric Aβ peptide into pathological aggregates remain unknown. Here, we show that the Aβ peptide can form biomolecular condensates on lipid bilayers both in molecular assays and in living cells.

Polygenic risk discriminates Lewy body dementia from Alzheimer's disease.

Introduction: Lewy body dementia (LBD) shares genetic risk factors with Alzheimer's disease (AD), including apolipoprotein E (APOE), but is distinguishable at the genome-wide level. Polygenic risk scores (PRS) may therefore improve diagnostic classification.

Methods: We assessed diagnostic classification using AD-PRS excluding APOE (AD-PRS ), APOE risk score (APOE-RS), and plasma phosphorylated tau 181 (p-tau181), in 83 participants with LBD, 27 with positron emission tomography amyloid beta (Aβ)positive mild cognitive impairment or AD (MCI+/AD), and 57 controls.

Role of NLRP3 Inflammasome in Chronic Pain and Alzheimer's Disease-A Review.

The coexistence of Alzheimer's disease (AD) and chronic pain (CP) in the elderly population has been extensively documented, and a growing body of evidence supports the potential interconnections between these two conditions. This comprehensive review explores the mechanisms by which CP may contribute to the development and progression of AD, with a particular focus on neuroinflammatory pathways and the role of microglia, as well as the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. The review proposes that prolonged pain processing in critical brain regions can dysregulate the activity of the NLRP3 inflammasome within microglia, leading to the overproduction of pro-inflammatory cytokines and excessive oxidative stress in these regions.

The molecular mechanism of nitric oxide in memory consolidation and its role in the pathogenesis of memory-related disorders.

Memory is a dynamic process of encoding, storing, and retrieving information. It includes sensory, short-term, and long-term memory, each with unique characteristics. Nitric oxide (NO) is a biological messenger synthesized on demand by neuronal nitric oxide synthase (nNOS) through a biochemical process initiated by glutamate binding to NMDA receptors, causing membrane depolarization and calcium influx.

Favorable long-term cognitive outcomes following recurrent ARIA linked to amyloid-lowering therapies: two cases.

Introduction: The large-scale approval of anti-amyloid monoclonal antibodies for treating Alzheimer's disease (AD) has raised concerns about their safety due to treatment-emergent amyloid-related imaging abnormalities (ARIA).

Methods: We present two cases of patients diagnosed with mild cognitive impairment due to AD who were enrolled in the GRADUATE I clinical trial. They received subcutaneous gantenerumab every two weeks during the study period.

Deep learning analyses of splicing variants identify the link of PCP4 with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease, with most sporadic cases lacking clear genetic causes. Abnormal pre-mRNA splicing is a fundamental mechanism in neurodegenerative diseases. For example, TAR DNA-binding protein 43 (TDP-43) loss-of-function (LOF) causes widespread RNA mis-splicing events in ALS.

Deep-Sea-Derived Isobisvertinol Targets TLR4 to Exhibit Neuroprotective Activity via Anti-Inflammatory and Ferroptosis-Inhibitory Effects.

Neuroinflammation and neuronal cell death are leading causes of death in the elderly and underlie various neurodegenerative diseases. These diseases involve complex pathophysiological mechanisms, including inflammatory responses, oxidative stress, and ferroptosis. Compounds derived from deep-sea fungi exhibit low toxicity and potent neuroprotective effects, offering a promising source for drug development.

New Insights into Chemical Profiles and Health-Promoting Effects of Edible Mushroom (Vent ex. Pers.) Fischer: A Review.

Mushrooms are valued for their culinary and medicinal benefits, containing bioactive compounds like polysaccharides, terpenoids, phenolics, lectins, and ergosterols. This review aims to encourage research on by summarizing its chemistry, health benefits, pharmacology, and potential therapeutic applications. Molecules from offer anti-diabetic, antioxidant, anti-tumor, hepatoprotective, and anti-bacterial effects.

Resonant Young's Slit Interferometer for Sensitive Detection of Low-Molecular-Weight Biomarkers.

The detection of low-molecular-weight biomarkers is essential for diagnosing and managing various diseases, including neurodegenerative conditions such as Alzheimer's disease. A biomarker's low molecular weight is a challenge for label-free optical modalities, as the phase change they detect is directly proportional to the mass bound on the sensor's surface. To address this challenge, we used a resonant Young's slit interferometer geometry and implemented several innovations, such as phase noise matching and optimisation of the fringe spacing, to maximise the signal-to-noise ratio.

Derivation and Characterization of Isogenic Mutant and Control Human Pluripotent Stem Cell Lines.

Dominant optic atrophy (DOA) is the most commonly inherited optic neuropathy. The majority of DOA is caused by mutations in the gene, which encodes a dynamin-related GTPase located to the mitochondrion. OPA1 has been shown to regulate mitochondrial dynamics and promote fusion.

Molecular Mechanisms of Alzheimer's Disease Induced by Amyloid-β and Tau Phosphorylation Along with RhoA Activity: Perspective of RhoA/Rho-Associated Protein Kinase Inhibitors for Neuronal Therapy.

Amyloid-β peptide (Aβ) is a critical cause of Alzheimer's disease (AD). It is generated from amyloid precursor protein (APP) through cleavages by β-secretase and γ-secretase. γ-Secretase, which includes presenilin, is regulated by several stimuli.

Modulation of Second Messenger Signaling in the Brain Through PDE4 and PDE5 Inhibition: Therapeutic Implications for Neurological Disorders.

Phosphodiesterase (PDE) enzymes regulate intracellular signaling pathways crucial for brain development and the pathophysiology of neurological disorders. Among the 11 PDE subtypes, PDE4 and PDE5 are particularly significant due to their regulation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling, respectively, which are vital for learning, memory, and neuroprotection. This review synthesizes current evidence on the roles of PDE4 and PDE5 in neurological health and disease, focusing on their regulation of second messenger pathways and their implications for brain function.

Examining Specific Theory-of-Mind Aspects in Amnestic and Non-Amnestic Mild Cognitive Impairment: Their Relationships with Sleep Duration and Cognitive Planning.

The study examined the relationships between specific Theory-of-Mind (ToM) dimensions, cognitive planning, and sleep duration in aging adults. The sample included 179 participants, comprising 46 cognitively healthy individuals, 75 diagnosed with amnestic Mild Cognitive Impairment (aMCI), and 58 with non-amnestic (naMCI). The mean age of the participants was 70.