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Brain interstitial fluid pharmacokinetics and therapeutic effect of a BBB penetrating amyloid beta antibody measured by microdialysis.

The disease-modifying antibody lecanemab for treating Alzheimer's disease (AD) was initially designed to target amyloid-beta (Aβ) protofibrils, i.e. soluble aggregates of Aβ, but it has also been successful in clearing insoluble amyloid plaques in clinical studies. Therefore, this study aimed to investigate how a brain penetrating, bispecific murine variant of lecanemab (RmAb158-scFv8D3) distributes in the brain and interacts with different pools of aggregated Aβ in APP transgenic mice. The alpha-synuclein targeting antibody RmAbSynO2-scFv8D3 was used as control. Further, by performing in vivo…

Spontaneous whole retinal degeneration in aged Beclin1 heterozygous mice.

Retinal degenerative diseases range from rare inherited forms to common multifactorial disorders such as age-related macular degeneration, which is the leading cause of blindness in developed countries. Recent evidence identifies impaired autophagy as a key pathogenetic mechanism. In the disease process alterations of the outer retina start from the retinal pigment epithelium (RPE), to progress downstream in the inner retina leading to widespread whole retinal degeneration. Recent studies indicate that among autophagy-related proteins Beclin1 plays a relevant effect in sustaining retinal integ

AQP4-mediated glymphatic clearance: Sleep, neurodegeneration, and the translational gap.

One-third of adults in industrialized societies are chronically sleep-deprived. If current evidence linking sleep disruption to glymphatic failure extends to human populations, this may represent not merely a productivity concern but a significant and underappreciated risk factor for neurodegeneration at the population scale. The glymphatic system, a brain-wide perivascular network that clears soluble amyloid-beta, tau, alpha-synuclein, and other neurotoxic metabolites through astrocytic aquaporin-4 water channels, operates predominantly during slow-wave sleep and is impaired when sleep is dis…

Missense mutations in the SNCA gene: Molecular mechanisms and clinical implications.

The SNCA gene on chromosome 4 encodes the alpha-synuclein (αSyn) protein, which plays a central role in the pathogenesis of synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). While αSyn has established roles in synaptic vesicle dynamics and neuronal signaling, alterations in SNCA regulation and sequence contribute to protein misfolding, aggregation, and loss of function. Alterations in secondary and tertiary structure, as well as protein aggregation, affect biochemical interactions, ultimately leading to pathogenesis. This…

Neuroprotective Parkinson's Disease Therapeutic: Transition Metal Dichalcogenide Nanoflower Treatments Alleviate Pathological Cell Stress.

Parkinson's disease (PD) is triggered by irreversible degeneration of dopaminergic neurons in the midbrain, hypothalamus, and thalamus. Although the underlying molecular etiology of these pathological processes remains unclear, progressive aggregation of alpha-synuclein (α-syn) and mitochondrial dysfunction are two expected mechanisms implicated in neuronal degeneration. Accumulating evidence indicates that transition metal dichalcogenide (TMD) nanoflowers (NFs), a novel class of nanomaterials, can restore mitochondrial health by the activation of mitochondrial biogenesis. However, therapeutic…

Multi-omics integration in disease research.

Neurodegenerative diseases, marked by complex molecular mechanisms and diverse clinical features, challenge conventional research approaches … ng errors in TARDBP-related ALS. Proteomics identifies key protein aggregates like amyloid beta and alpha-synuclein, along with modifications such as hyperphosphorylated tau that correlate with cognitive decline. Metabolomics uncovers metabolic alterations, including mitochondrial dysfunction in Parkinson's and lipid peroxidation in ALS, which contribute to disea …

Alzheimer Combination Therapies: Overview and Scenarios.

Progress in understanding the complexity of Alzheimer's disease informs the search for combination therapies that can successfully prevent o … ed processes include tau abnormalities, inflammation, neurodegeneration, and co-pathologies such as alpha-synuclein and TDP-43. The choice of combination therapies will depend on the strength of the information regarding the target, biomarkers to guide clinical trials, and a candidate agent with the appropriate mechanism of action. Computational strategies based …

Current Perspectives in Detection of Bioactive Compounds From Costus spicatus Through GC-MS and LC-MS/MS: Antioxidant Properties and In Silico Analysis for Industrial Applications.

Members of the Costus genus are the conventional medicinal plants used in the therapeutic management of numerous ailments, especially for th … nd found that four compounds exhibited promising binding affinities with predicted binding sites on alpha-synuclein. Notably, Androsta [17-16-b] furan-5'-imine, 4'-methylene-3-methoxy-N-cyclohexyl- showed the highest docking interaction score of -7.4, indicating a strong binding affinity. These findings, combined with the presence of bioactive components in the c …

High Selectivity Fluorescence and Electrochemical Dual-Mode Detection of Glutathione in the Serum of Parkinson's Disease Model Mice and Humans.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of alpha-synuclein. Glutathione (GSH), a key antioxidant, is significantly depleted in PD patients. This study presents a dual-mode detection strategy for selectively determining GSH using a single probe. A series of "turn-on" electrochemical and fluorescent probes were developed, with resorufin (Re) serving as the reporting unit and featuring specific GSH recognition sites. Among these, the 7-(3,5-dinitrophenoxy)-3H-phenoxazin-3-one (Re-DNP) probe was sel…

Long-term Neurological Consequences of COVID-19 in Patients With Pre-existing Alzheimer's and Parkinson's Disease: A Comprehensive Review.

SARS-CoV-2, the causative agent of COVID-19, has profound systemic effects, including significant impacts on the central nervous system (CNS … infection influences proteinopathies by accelerating the aggregation of pathological proteins like alpha-synuclein, tau, and TDP-43, contributing to disease progression in PD, AD, and related disorders. Clinical studies reporting cognitive and motor dysfunctions in post-COVID-19 patients with pre-existing neurodegenerative diseases are also summarized. Finally, …

Использование микробиомных средств для совершенствования методов лечения нейродегенеративных заболеваний: данные о воздействии вдоль оси микробиота-гут-мозгов.

Недавно в качестве полезной модели для понимания возникновения и развития нейродегенеративных заболеваний (НДД) появилась ось микробиота-гут-мозгов (МГБА). Меры воздействия на основе микробиома с использованием биотических добавок (пробиотики, предбиотики, синдиотики, постбиотики) могут модифицировать MGBA и служить подходящими решениями для снижения риска неврологических изменений, связанных с НИЗ, и регулирования симптомов. В настоящем описательном обзоре содержится резюме функционирования МГБС и его взаимодействия с заболеваниями, связанными с началом и развитием НИЗ. Проводится обзор мероп

Совпадение в аннотации оригинала
The microbiota-gut-brain axis (MGBA) has recently emerged as a useful model for the understanding of the onset and progression of neurodegen … ton's disease (HD) are reviewed. Evidence related to biomarkers of pathology (e.g., beta-amyloid or alpha-synuclein protein depositions), neuroinflammation, and metabolic activity is summarized, along with emerging evidence for the improvement of clinical symptoms and disease trajectories. Overall, preclinical studies show that microbiome-based supplements have s …

A bibliometric analysis of acupuncture for Parkinson's disease non-motor symptoms from 2003 to 2023.

BACKGROUND: Parkinson's disease non-motor symptoms (PD-NMS) significantly affect patients' quality of life. Acupuncture has emerged as a pot … ons. The keyword analysis highlighted emerging areas of interest like "deep brain stimulation" and "alpha-synuclein". CONCLUSION: Different countries, institutions, and authors should enhance cooperations, and the underlying mechanisms of acupuncture for PD-NMS should be demonstrated. This study will be helpful for better understanding the current knowledge and …

Genetics of Multiple System Atrophy and Progressive Supranuclear Palsy: A Systemized Review of the Literature.

Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are uncommon multifactorial atypical Parkinsonian syndromes, expressed by various clinical features. MSA and PSP are commonly considered sporadic neurodegenerative disorders; however, our understanding is improving of their genetic framework. The purpose of this study was to critically review the genetics of MSA and PSP and their involvement in the pathogenesis. A systemized literature search of PubMed and MEDLINE was performed up to 1 January 2023. Narrative synthesis of the results was undertaken. In total, 43 studies wer

Tuberous sclerosis complex is associated with a novel human tauopathy.

Tuberous sclerosis complex (TSC) is a neurogenetic disorder leading to epilepsy, developmental delay, and neurobehavioral dysfunction. The s … gical controls. This tauopathy was observed in the absence of pathological amyloid beta, TDP-43, or alpha-synuclein deposition. The neurofibrillary tangles in TSC tauopathy showed a unique pattern of post-translational modifications, with apparent differences between TSC1 and TSC2 mutation carriers. Tau acetylation (K274, K343) was prominent in both TSC1 and TSC2 …

Genetic Analysis and Literature Review of SNCA Variants in Parkinson's Disease.

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder. Aging, environmental factors, and genetics are considered as risk factors. The alpha-synuclein gene (SNCA), the first pathogenic gene identified in a familial form of PD, was indisputably involved as a heritable component for familial and sporadic PD. In this study, whole-exome sequencing and Sanger sequencing were performed to evaluate the association between the SNCA gene variants and PD. The genetic data of 438 clinically diagnosed patients with PD and 543 matched control populations of the Han Chinese were analyzed…

Independent effect of neurogenic orthostatic hypotension on mild cognitive impairment in Parkinson's disease.

PURPOSE: Orthostatic hypotension (OH) is an associative or causative factor of cognitive impairment in Parkinson's disease (PD). However, the association between mild cognitive impairment (MCI) and neurogenic OH directly associated with the presence of alpha-synuclein in PD remains unclear. We aimed to evaluate the relationship between MCI and neurogenic OH in patients with de novo PD. We also investigated the patterns of neuropsychological performance according to neurogenic OH. METHODS: A total of 456 patients with PD-normal cognition (PD-NC, n = 204) or PD-MCI (n = 252) were recruited from…

The supraoptic and paraventricular nuclei in healthy aging and neurodegeneration.

The supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus undergo structural and functional changes over the course of healt … brain regions, while the SON is relatively spared. In contrast, the SON appears more vulnerable to alpha-synuclein pathology of DLB and PD. The consequences of these alterations may help to inform several of the physiologic changes observed in aging and neurodegenerative disease.

From the Cover: Alterations in Optineurin Expression and Localization in Pre-clinical Parkinson's Disease Models.

Parkinson's disease (PD) is a progressive neurodegenerative disease that affects ∼5 million people around the world. PD etiopathogenesis is … nt on duration of treatment. Furthermore, OPTN colocalizes with LC3 (autophagic vesicle marker) and alpha-synuclein positive puncta in rotenone-treated animals, potentially indicating an important role in autophagy and PD pathogenesis.

Creation of a library of induced pluripotent stem cells from Parkinsonian patients.

Induced pluripotent stem cells (iPSCs) are becoming an important source of pre-clinical models for research focusing on neurodegeneration. T … r neuron disease amyotrophic lateral sclerosis (ALS), while mutations in the SNCA gene encoding for alpha-synuclein protein lead to familial Parkinson's disease (PD). The generations of libraries of familial human ALS iPSC lines have been described, and the iPSCs rapidly became useful models for studying cell autonomous and non-cell autonomous mechanisms of the d …

Monogenic Parkinson's disease and parkinsonism: clinical phenotypes and frequencies of known mutations.

Mutations in seven genes are robustly associated with autosomal dominant (SNCA, LRRK2, EIF4G1, VPS35) or recessive (parkin/PARK2, PINK1, DJ1 … A cause cognitive or psychiatric symptoms, parkinsonism, dysautonomia and myoclonus with widespread alpha-synuclein pathology in the central and peripheral nervous system. LRRK2 mutations may lead to a clinical phenotype closely resembling idiopathic PD with a puzzling variety in neuropathology. Mutations in parkin/PARK2, PINK1 or DJ1/PARK7 may cause early-onset …