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Fluorescence as a method to reveal structures and membrane-interactions of amyloidogenic proteins.

Amyloidogenesis is a characteristic feature of the 40 or so known protein deposition diseases, and accumulating evidence strongly suggests t … here. Amyloidogenic proteins discussed include A-beta from Alzheimer's disease, the prion protein, alpha-synuclein from Parkinson's disease, transthyretin (FAP, SSA amyloidosis), immunoglobulin light chains (primary (AL) amyloidosis), serum amyloid A (secondary (AA) amyloidosis), amylin or IAPP (Type 2 diabetes) and apolipoproteins. This review highlights the si …

Serofendic acid prevents 6-hydroxydopamine-induced nigral neurodegeneration and drug-induced rotational asymmetry in hemi-parkinsonian rats.

Serofendic acid was recently identified as a neuroprotective factor from fetal calf serum. This study was designed to evaluate the neuroprot … the results in vehicle-treated control rats. In addition, serofendic acid inhibited 6-OHDA-induced alpha-synuclein expression and glial activation in the SNpc. These results suggest that serofendic acid protects against 6-OHDA-induced SNpc dopaminergic neurodegeneration in a rat model of Parkinson's disease.

[Familial non-Alzheimer dementia].

This is an abstract of my lecture on familial non-Alzheimer dementia. 1. Vascular dementia 1) Cerebral autosomal dominant arteriopathy with … eimer like dementia, visual hallucination and diffuse Lewy bodies which are formed by ubiquitinated alpha-synuclein. Occasionally, familial forms are reported, but gene mutations are unknown. 2) Frontotemporal dementia (FTD) FTDP-17 is characterized by tau mutations, character and personal changes, and disinhibition. The gene mutations were also found in familial …

Cutaneous phosphorylated-synuclein: an early diagnostic biomarker for pure autonomic failure.

BACKGROUND: Pure autonomic failure (PAF) presents with progressive autonomic failure without other neurological features. Atypical presentations may lead to diagnostic uncertainty. We studied whether cutaneous phosphorylated-alpha-synuclein (p-syn) could distinguish between PAF, multiple system atrophy (MSA) and non-synucleinopathy-related autonomic failure, and examined its relationship with quantitative markers of cardiovascular autonomic failure. METHODS: All individuals underwent Composite Autonomic Symptom Score-31 autonomic questionnaires, cardiovascular autonomic testing and bilateral …

The neurological mutant quaking(viable) is Parkin deficient.

The mouse mutant quaking(viable) ( qk(v)) has been studied for almost four decades as a model for dysmyelination of the central nervous syst … n qk(v) brains does not result in the loss of dopaminergic neurons typical of AR-JP patients. Also, alpha-synuclein, a target of Parkin-dependent ubiquitination, does not accumulate in qk(v) mutant brains. Despite the lack of AR-JP-like neuropathology in qk(v) mice, this mutant may constitute a readily available model for the study of the cellular function of Par …

Targeting protein misfolding and aggregation in neurodegenerative diseases: challenges for the identification and validation of targets for small molecules.

INTRODUCTION: Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), an … in major neurodegenerative proteinopathies, including amyloid-beta and tau in Alzheimer's disease, alpha-synuclein in synucleinopathies, TDP-43 and FUS in ALS/FTLD, polyglutamine-expanded proteins, prion proteins, and rare hereditary amyloidosis. We also discuss major barriers to target identification and validation, including conformational flexibility, oligome …

Regional gene expression and brain atrophy in dementia with Lewy bodies: an imaging transcriptomics study.

Regional brain atrophy has been observed in dementia with Lewy bodies (DLB), yet determinants of regional vulnerability remain unclear. Using imaging transcriptomics, we examined whether normative gene expression patterns relate to regional atrophy in DLB. We included 164 DLB patients (49 women) and 164 age- and sex-matched healthy controls from three European centres and the Mayo Clinic, USA. Volumetric atrophy was quantified from T1-weighted MRI across 58 left-hemispheric regions using w-scores. Normative expression of twelve genes implicated in alpha-synuclein, beta-amyloid, and tau patholo…

Hydroxytyrosol as a Multitarget Neuroprotective Agent: Molecular Mechanisms, Pharmacokinetics and Therapeutic Potential in Neurodegenerative Diseases.

Neurodegenerative diseases arise from interacting oxidative, inflammatory, mitochondrial, and proteostatic disturbances. Hydroxytyrosol (HT), an olive phenol, has been proposed as a multitarget neuroprotective compound. This narrative review integrates HT chemistry, parent/metabolite pharmacokinetics, blood-brain barrier (BBB) evidence, mechanisms, disorder-specific models, and human studies. Direct HT evidence is strongest for nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) activation and experimental modulation of α-synuclein; support for AMP-activated pro

Narrative Review of Body-First Versus Brain-First Prodromal Neuropsychiatric Symptoms in Parkinson's Disease.

Parkinson's disease (PD) is a multisystem neurodegenerative disorder in which nonmotor symptoms often precede classical motor manifestations … lar between 2003 and 2025 using terms related to PD, prodromal symptoms, neuropsychiatric symptoms, alpha-synuclein, and body-first versus brain-first disease. Priority was given to review articles, original studies, clinical trials, Movement Disorder Society prodromal criteria, and foundational neuropathological models. Current evidence supports a dual pathway m …

Retinoid X Receptor as a Therapeutic Target to Treat Neurological Disorders Associated with α-Synucleinopathy.

This study investigated the therapeutic potential of the nuclear retinoid X receptor (RXR) in mitigating the progression of alpha-synucleinopathies (αSNPs), particularly in Parkinson's disease (PD). PD-like pathology in mice was successfully induced through the co-delivery of AAV expressing human α-synuclein (αS) and αS preformed fibrils (PFFs) into the substantia nigra pars compacta (SNpc). Significant increases in Lewy body (LB)-like inclusions, loss of tyrosine hydroxylase-positive (TH+) neurons, and reductions in dopamine (DA) levels in the striatum were observed. Additionally, diminished …

Identification of exosome-related gene biomarkers for parkinson's disease: a multi-omics approach for early diagnosis and therapeutic targeting.

Parkinson’s disease (PD) is a neurodegenerative disorder linked to alpha-synuclein pathology and dopaminergic neuron loss. Exosomes play dual roles in PD progression, facilitating pathological protein spread or exerting neuroprotective effects. This study aimed to identify exosome-related gene biomarkers for PD diagnosis and therapy. Using multi-dataset analysis (Series: GSE42966, Platforms: GPL4133, Series: GSE99039, Platforms: GPL570, Series: GSE156926, Platforms: GPL19920) from the Gene Expression Omnibus (GEO), we integrated principal component analysis (PCA), differential gene screening (…

Electroacupuncture Regulates Mitochondria-Endoplasmic Reticulum interactions via Fn1 in a Parkinson's Disease Model: Transcriptomic Evidence.

AIMS: Parkinson's disease (PD) is characterized by dopaminergic neuron degeneration and disruption to mitochondria-associated endoplasmic re … rformance, increased substantia nigra (SN) and striatum tyrosine hydroxylase expression, reduced SN alpha-synuclein, and improved SN dopamine neuron MAM structure. Transcriptomic analysis identified 32 MAM-associated genes, of which fibronectin-1 (Fn1) was identified as a key regulator. EA was found to upregulate Fn1 expression, suggesting its involvement in MAM …

Brain injury contributes to dopaminergic neurodegeneration, Lewy body pathology, and Parkinsonism preclinically with outcomes altered by T cell modulation.

Traumatic brain injury (TBI) increases the risk of Parkinson's disease (PD) development later in life, but much remains unknown regarding the mechanisms driving this relationship. A single, mild brain injury triggers resident and peripheral neuroinflammatory pathways that are similarly activated in PD patients, which could possibly increase susceptibility to neurodegeneration. In this study, we used preclinical mouse models of mild TBI (mTBI) and PD to evaluate how injury-induced immune signaling may exacerbate PD-associated pathologies. Dopaminergic (DA) neurons showed upregulation of genes a

Искусственные разведывательные методологии для ранней диагностики точности и индивидуализированных терапевтических стратегий в нейро-офтальмических и нейродегенеративных патологиях.

Совершенствование нейроимации, в частности методов диффузной магнитной резонансной съемки (MRI) и молекулярной съемки с помощью позитронной томографии (ПТЭ), значительно повысило раннее обнаружение биомаркеров в нейродегенеративных и нейро-офтальмических расстройствах. К ним относятся болезнь Альцгеймера, болезнь Паркинсона, множественный склероз, оптика нейромиелита и болезнь антител миэлина олигодендроцита гликопротеина. В настоящем обзоре подчеркивается преобразующая роль современных методов диффузии MRI - Неевритная ориентация - диспергация и интерпретация плотности и дифлюстрация Куртоза

Совпадение в аннотации оригинала
Advancements in neuroimaging, particularly diffusion magnetic resonance imaging (MRI) techniques and molecular imaging with positron emissio … flammation. Additionally, next-generation PET tracers targeting misfolded proteins, such as tau and alpha-synuclein, along with inflammatory markers, enhance the visualization and quantification of pathological processes in vivo. Deep learning models, including convolutional neural networks and multimodal transformers, further improve diagnostic accuracy by integ …

Research progress in the molecular mechanism of ferroptosis in Parkinson's disease and regulation by natural plant products.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder of the central nervous system after Alzheimer's disease. The current understanding of PD focuses mainly on the loss of dopamine neurons in the substantia nigra region of the midbrain, which is attributed to factors such as oxidative stress, alpha-synuclein aggregation, neuroinflammation, and mitochondrial dysfunction. These factors together contribute to the PD phenotype. Recent studies on PD pathology have introduced a new form of cell death known as ferroptosis. Pathological changes closely linked with ferroptos…

Evaluation of putative CSF biomarkers in paediatric spinal muscular atrophy (SMA) patients before and during treatment with nusinersen.

Spinal muscular atrophy (SMA) is a genetic neurodegenerative disorder leading to immobilization and premature death. Currently, three altern … ), light-chain neurofilaments (NfL), total tau protein (T-Tau), neurogranin, β-secretase BACE-1 and alpha-synuclein) in 193 CSF samples of 44 paediatric SMA types 1, 2 and 3 patients before and under nusinersen treatment and related them to standardized clinical outcome scores in a single-centre pilot study. pNf-H and NfL correlated with disease severity and acti …

miR-7 Replacement Therapy in Parkinson's Disease.

The present review examines whether the microRNA 7 (miR-7) holds potential for slowing Parkinson's disease (PD) progression. First, the accurate expression of miR-7 allows for normal development, physiology, and neurogenesis in the central nervous system, also keeping alpha-synuclein (α-Syn) at the physiological level. Second, patients with PD and parkinsonian MPTP-induced animals exhibit a significant decrease of miR-7 in brain areas associated with dopaminergic neurodegeneration. Depletion of miR-7 in the substantia nigra of clinical samples is related to α-Syn accumulation, loss of dopamine…

Orthostatic hypotension and cardiac sympathetic denervation in Parkinson disease patients with REM sleep behavioral disorder.

BACKGROUND: Rapid eye movement (REM) sleep behavioral disorder (RBD), orthostatic hypotension (OH), and cardiac sympathetic denervation were … ation could be the mechanism behind OH in PD. This association may be closely correlated with Braak alpha-synuclein pathogenetic sequences, which would account for the clinical spectrum of PD.

Glucocerebrosidase deficiency and mitochondrial impairment in experimental Parkinson disease.

Gaucher disease is an autosomal recessive disease, caused by a lack or functional deficiency of the lysosomal enzyme, glucocerebrosidase (GC … ase activity may render dopaminergic neurons susceptible to MPP(+) (1-methyl-4-phenylpyridinium) or alpha-synuclein (α-Syn) toxicity and amenable to miglustat treatment. We could demonstrate that reduction of glucocerebroside by inhibition of glucosylceramide synthase partially protects mice against MPTP-induced toxicity. Conversely, we could show that inhibition …

[Atypical parkinsonism].

BACKGROUND: The dopamine deficiency syndrome Parkinson's disease (PD) is characterized by tremor, rigidity, bradykinesia and reduced postural reflexes. Conditions with similar symptoms but other causes than PD (about 1/3 of cases) are called atypical parkinsonism. From a neuropathological perspective, PD is associated with loss of nigro-striatal dopaminergic neurons (related to motor symptoms) and accumulation of alpha-synuclein-containing Lewy bodies in the mid-brain. Nigro-striatal pathways may also be involved in atypical parkinsonism, but lesions in other parts of the brain/basal ganglions…