Α-synuclein

…widespread intracellular inclusions of α-synuclein known as Lewy bodies. Evidence suggests that these misfolded protein inclusions spread through the brain with disease progression. Changes in synaptic function precede neurodegeneration, and this extracellular α-synuclein can affect synaptic transmission. However, whether and how the spreading of α-synuclein aggregates modulates synaptic function before neuronal loss remains unknown. In the present study, we investigated the effect of intrastriatal injection of α-synuc

…nigra, and it has been reported that α-synuclein accumulates in the gut and then affects the brain along the gut-brain axis. In this study, we used Enterococcus faecium (EF), which was probiotics, that confer health benefits on the host when administered in adequate amounts. C57BL/6 mice, a model of PD induced by MPTP, were treated with EF (1ⅹ1012 CFU/mL). The study showed that motor dysfunction in MPTP-induced PD model mice improved. Additionally, EF was found to decrease the accumulation o

…of Alzheimer's disease (AD), and α-synuclein, the major protein of Lewy bodies in Parkinson's disease (PD), may interact with transcription factors and affect gene transcription. Researchers have revealed that Aβ1-42 can be found in the nucleus, interact with DNA, and change the expression of many genes. It is known that α-synuclein functions as a transcription factor that binds to nuclear DNA and modulates the expression of many genes. Our study aims to investigate whether these peptides directly affect the expression of

…Characterization of α-Synuclein (α-Syn) oligomeric species was performed using ThT fluorescence, SDS-PAGE, DLS, and microscopy. Cell culture assays measured viability, cytotoxicity, and intracellular seeding in transgenic cell models. In vivo experiments were conducted in transgenic C. elegans.Results: T

…of proteins like Aβ, TDP-43 and α-synuclein. For this, a complete physicochemical characterization of soy lecithin and other raw materials was carried

…is challenging due to the lack of α-synucleinopathy animal models that do not also develop Parkinsonism. To address this issue, we have developed a new mouse model for investigating the impact of α-synuclein (α-Syn) overexpression and aggregation on driving cortical and hippocampal circuit dysfunction. Using bilateral stereotaxic injections of adeno-associated virus (AAVs) vectors, we transduced overexpression of human SNCA (encoding α-Syn) with mScarlet (red fluorophore), or an mScarlet-only control vector. We targeted either dorsal hi

Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by resting tremor, rigidity, and bradykinesia. Additionally, a wide spectrum of early non-motor symptoms has been described, among which cognitive impairment is one of the most relevant.Several studies show that interventions focused on cognitive stimulation can play an important role in preventing or delaying the onset of dementia in patients with neurodegenerative diseases. In this perspective, we aimed at investigating the synaptic mechanisms mediating the effects of cognitive enrichment in two mouse models

…They have been shown to spread α-synuclein (αSyn) – the main pathological hallmark of Parkinson´s disease (PD) – and miRNAs that can influence the expression of genes associated with PD progression. On this basis, they are becoming interesting as diagnostic biomarkers. So far, however, data from patients are heterogeneous and inconsistent. Therefore, we aim to use a cellular model that allows us to investigate the role of EVs in PD pathology on a homogeneous genetic

Understanding the neurodevelopment of cerebellar nuclei (CN), the primary output of the cerebellum, is crucial. Traditionally, the rhombic lip (RL) and ventricular zone (VZ) have been known as the origins of glutamatergic excitatory and GABAergic inhibitory CN neurons, which emerge after embryonic day 9 (E9). However, our study uncovers a novel subset of cells in the nuclear transitory zone (NTZ), a transient area for future CN that appears even before E9. Our study’s objective is to map the fate of these early-appearing cells in the developing cerebellum. Utilizing SncaGFP transgenic mice, th

…PD, particularly lewy’s bodies and α-synuclein, and increased the number of tyrosine hydroxylase positive cells. G

…of proteinaceous aggregates of α-synuclein (α-syn) in cell bodies and neurites of Substantia Nigra pars compacta (SNpc) dopaminergic neurons, eventually causing cell death. Interestingly, defective activity or mutations in GBA1, the gene encoding the lysosomal enzyme Glucocerebrosidase (GCase), are the strongest risk factor to develop PD. Based on this evidence, reverting the cytological and molecular abnormalities caused by GCase mutations or enhancing the activity of the wild type enzyme may represent a feasible therapeut

Aging leads to the accumulation of misfolded proteins, such as β-amyloid and α-synuclein, which are believed to underly the onset of neurodegenerative disorders. Most of the treatments for brain disorders come from pre-clinical evidence in males, although women are more vulnerable than men to Alzheimer’ disease (AD) which is the first cause of age-related dementia. However, the mechanisms underlying these sex-differences are not known.To date, two therapeutic approaches are predominantly used to prevent and/or slow neurodegeneration; they include autophagy pharmacological enhancers and exercis

Due to its association with the chromosomal region PARK12, Interleukin-13 receptor alpha 1 (IL-13Rα1) is anticipated to play a role in the pathology of Parkinson's disease (PD). Elevated IL-13 levels within the substantia nigra (SN) during chronic stress, coupled with the expression of IL-13Rα1 in dopaminergic neurons, suggest their potential involvement in neurodegenerative processes. However, the role of IL-13Rα1 in the pathological state of PD remains unclear. We investigated IL-13Rα1 expression patterns in postmortem brain tissues from PD patients and age-matched controls using western blo

…by pathogenic deposition of α-synuclein-laden Lewy bodies within vulnerable neurons, including those of the hippocampus (HC). The strongest risk factor for sporadic Alzheimer’s disease (AD), and recently demonstrated for DLB, is the ε4 allele of apolipoprotein (APOE4) that is a major lipoprotein in the central nervous system playing a leading role in maintaining lipid homeostasis. Our group recently demonstrated that the APOE4 aggravates cognitive deficits in a mouse model of prodromal DLB – corrob

Dementia with Lewy Bodies (DLB) is caused by aggregation of insoluble α-synuclein (α-syn) in neurons and patients exhibit cognitive impairment involving the anterior cingulate cortex (ACC). Parvalbumin-expressing interneurons (PVIs) are critical for normal cognitive function and are often surrounded by a specialised extracellular matrix, the perineuronal nets (PNNs). Loss of PVIs and PNNs occurs in Alzheimer’s disease but their role in DLB remains unclear. In addition, neuroinflammatory changes may also play an early role in DLB. Using transgenic mice expressing human mutant α-syn (hA30P), we

…to Parkinson’s disease, and exogenous α-synuclein fibrils spread from the gut to brain via the vagus nerve in animal models. However, the natural cause of enteric α-synuclein pathology is unknown, but emerging research implicates enteroendocrine cells in the gut epithelium. We investigated epithelial α-synuclein through confocal microscopy and western blotting of human intestinal epithelial monolayers (Aim 1), and imaging flow cytometry of murine enteroendocrine STC-1 cells (Aim 2). Aim 1 d

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by movement disorders. The main characteristic of PD is the loss or degeneration of dopaminergic neurons in the substantia nigra. The gut microbiota is now recognized as a potential participant in the pathogenesis of PD. This study aims to investigate the effects of Lactobacillus sakei (Ls) on the gut-brain axis and explore the underlying molecular mechanism using a PD model. Probiotics were orally administered for four weeks after MPTP injection. The study observed that Ls significantly improved movement, includi

Aims: α-synuclein is a protein that is highly expressed in brain neurons. Its normal function is still unknown, but it is thought to be crucial to the onset of dementia with Lewy bodies (DLB). As of now, DLB cannot be sufficiently explained by mutations in the α-synuclein protein because there are so few α-synuclein mutations found in DLB. Nevertheless, several studies have revealed that individuals with DLB also co-exhibit Aβ accumulation in the brain, suggesting that Aβ could be involved in α-synuclein neurotoxicity. However, the exact molecular mechanism behind Aβ-induced α-synuclein toxici

Under normal conditions, α-synuclein (αS) is preferentially localized within synaptic boutons. Changes in αS localization may occur, however, as a consequence of a variety of pathophysiological conditions that include increased protein expression. The purpose of this study was to investigate intraneuronal sites of overexpression-induced αS accumulation. In particular, we assessed αS burden within neuronal perikarya and nuclei; the latter analysis was facilitated by a newly developed assay that detected interactions between αS and histones.Experiments were carried out in the substantia pars com

Transmission of misfolded α-synuclein between neurons is a key mechanistic feature of Parkinson’s and in the creation of Lewy pathology. Despite the prion-like nature of Parkinson’s, it is not yet known why some cell populations are resistant to pathology development. We hypothesise that an extracellular neuronal coat, the perineuronal net (PNN), could be a factor underlying neuronal resistance in Parkinson’s. A proteomic screen of extracellular brain lysate with PNN-derived glycans identified the entire synuclein family. Using surface plasmon resonance, the PNN glycans, heparin sulfate &

…line G2-3, which over-express human α-synuclein and are the only model of PD that exhibits prodromal constipation. Additionally, we investigated whether sharing social microenvironmen

Pain is considered one of the most frequent non-motor symptoms of Parkinson’s disease (PD) and it usually manifests before the motor symptoms. Although not considered one of the cardinal symptoms of PD, pain affects up to 80% of PD patients and half of them report multiple types of pain. The cause of this pain is still unknown, but it may be due to dysfunction of key nuclei in the processing of nociceptive information.In order to determine the possible causes of this prodromal symptom, we use different parkinsonian models, such as the hα- syn1-120 model, which presents a differential expressio

Parkinson's disease (PD) is a complex pathology presenting with motor symptoms coupled with a variety of non-motor symptoms originating in the central nervous system or the periphery, resulting in a complex multisystem disease. The development of therapeutic approaches to slow or stop disease progression remains the greatest unmet therapeutic need for PD. The immune system plays a pivotal role in the central and peripheral pathology of PD, reacting to misfolded α‐synuclein with neuroinflammation and dysregulation of peripheral immune responses. Here, we tested the neuroprotective properties of

α-Synuclein (α-Syn) and Tau proteins are neuropathological hallmarks for synucleinopathies and tauopathies, respectively. Co-occurrence of a-Syn and tau aggregates was found in the post-mortem brains of the patients, suggesting a complex interplay between two proteins contributes to the diseases. Here, we explore the polymorphism of α-Syn and Tau cross-seeding with a correlative approach combining fluorescent and super-resolution optical photothermal infrared (O-PTIR) imaging. We first show that hybrid α-Syn-Tau 0N3R pre-formed fibrils (PFFs) form more amyloid-rich structures than α-Syn or a-S