TopicNeuroscience

Synuclein

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46Total items

40ePosters

6Seminars

Latest

SeminarNeuroscience

The synaptic functions of Alpha Synuclein and Lrrk2

Subhojit Roy, MD, PhD

University of Wisconsin-Madison

Feb 18, 2025

Alpha synuclein and Lrrk2 are key players in Parkinson's disease and related disorders, but their normal role has been confusing and controversial. Data from acute gene-editing based knockdown, followed by functional assays, will be presented.

SeminarNeuroscience

Alpha synuclein in parkinson's Disease: From the bedside to the bench and back again

Stefanis Leonidas

Medical School, National and Kapodistrian University of Athens and Biomedical Research Foundation of the Academy of Athens, Athens, Greece

Jan 31, 2024

SeminarNeuroscience

Multimodal imaging in Dementia with Lewy bodies

Kejal Kantarci

Mayo Clinic

Feb 14, 2022

Dementia with Lewy bodies (DLB) is a synucleinopathy but more than half of patients with DLB also have varying degrees of tau and amyloid-β co-pathology. Identifying and tracking the pathologic heterogeneity of DLB with multi-modal biomarkers is critical for the design of clinical trials that target each pathology early in the disease at a time when prevention or delaying the transition to dementia is possible. Furthermore, longitudinal evaluation of multi-modal biomarkers contributes to our understanding of the type and extent of the pathologic progression and serves to characterize the temporal emergence of the associated phenotypic expression. This talk will focus on the utility of multi-modal imaging in DLB.

SeminarNeuroscience

Multimorbidity in the ageing human brain: lessons from neuropathological assessment

Kirsty McAleese

Newcastle University

Jun 8, 2021

Age-associated dementias are neuropathologically characterized by the identification of hallmark intracellular and extracellular deposition of proteins, i.e., hyperphosphorylated-tau, amyloid-β, and α-synuclein, or cerebrovascular lesions. The neuropathological assessment and staging of these pathologies allows for a diagnosis of a distinct disease, e.g., amyloid-β plaques and hyperphosphorylated tau pathology in Alzheimer's disease. Neuropathological assessment in large scale cohorts, such as the UK’s Brains for Dementia Research (BDR) programme, has made it increasingly clear that the ageing brain is characterized by the presence of multiple age-associated pathologies rather than just the ‘pure’ hallmark lesion as commonly perceived. These additional pathologies can range from low/intermediate levels, that are assumed to have little if any clinical significance, to a full-blown mixed disease where there is the presence of two distinct diseases. In our recent paper (McAleese et al. 2021 Concomitant neurodegenerative pathologies contribute to the transition from mild cognitive impairment to dementia, https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12291, Alzheimer's & Dementia), using the BDR cohort, we investigated the frequency of multimorbidity and specifically investigated the impact of additional low-level pathology on cognition. In this study, of 670 donated post-mortem brains, we found that almost 70% of cases exhibited multimorbidity and only 22% were considered a pure diagnosis. Importantly, no case of Lewy Body dementia or vascular dementia was considered pure. A key finding is that the presence of low levels of additional pathology increased the likelihood of having mild dementia vs mild cognitive impairment by almost 20-fold, indicating low levels of additional pathology do impact the clinical progression of a distinct disease. Given the high prevalence and the potential clinical impact, cerebral multimorbidity should be at the forefront of consideration in dementia research.

SeminarNeuroscience

Targeting selective autophagy against neurodegenerative diseases

Ana Maria Cuervo

Albert Einstein College of Medicine, New York, USA

Apr 21, 2021

Protein quality control is essential for maintenance of a healthy and functional proteome that can attend the multiplicity of cellular functions. Failure of the systems that contribute to protein homeostasis, the so called proteostasis networks, have been identified in the pathogenesis of multiple neurodegenerative disorders and demonstrated to contribute to disease onset and progression. We are interested in autophagy, one of the components of the proteostasis network, and in the interplay of wo selective types of autophagy, chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI), with neurodegeneration. We have recently found that pathogenic proteins involved in common neurodegenerative conditions such as tauopathies or Parkinson’s disease, can exert a toxic effect in both types of selective types of autophagy compromising their functioning. We have now used mouse models with compromised CMA that support increased propagation of proteins such as tau and alpha-synuclein and an exacerbation of disease phenotype with aging. Conversely, genetic or chemical upregulation of CMA in this context of proteotoxicity slow down disease progression by facilitating effective intracellular removal of pathogenic proteins. Our findings highlight CMA and eMI as potential novel therapeutic targets against neurodegeneration.

SeminarNeuroscience

Neurotoxicity is a major health problem in Africa: focus on Parkinson's / Parkinsonism

Nouria Lakhdar-Ghazal

Mohammed V University, Morocco

Oct 22, 2020

Parkinson's disease (PD) is the second most present neurodegenerative disease in the world after Alzheimer's. It is due to the progressive and irreversible loss of dopaminergic neurons of the substantia nigra Pars Compacta. Alpha synuclein deposits and the appearance of Lewi bodies are systematically associated with it. PD is characterized by four cardinal motor symptoms: bradykinesia / akinesia, rigidity, postural instability and tremors at rest. These symptoms appear when 80% of the dopaminergic endings disappear in the striatum. According to Braak's theory, non-motor symptoms appear much earlier and this is particularly the case with anxiety, depression, anhedonia, and sleep disturbances. In 90 to 95% of cases, the causes of the appearance of the disease remain unknown, but polluting toxic molecules are incriminated more and more. In Africa, neurodegenerative diseases of the Parkinson's type are increasingly present and a parallel seems to exist between the increase in cases and the presence of toxic and polluting products such as metals. My Web conference will focus on this aspect, i.e. present experimental arguments which reinforce the hypothesis of the incrimination of these pollutants in the incidence of Parkinson's disease and / or Parkinsonism. Among the lines of research that we have developed in my laboratory in Rabat, Morocco, I have chosen this one knowing that many of our PhD students and IBRO Alumni are working or trying to develop scientific research on neurotoxicity in correlation with pathologies of the brain.

Synuclein

Latest

The synaptic functions of Alpha Synuclein and Lrrk2

Alpha synuclein in parkinson's Disease: From the bedside to the bench and back again

Multimodal imaging in Dementia with Lewy bodies

Multimorbidity in the ageing human brain: lessons from neuropathological assessment

Targeting selective autophagy against neurodegenerative diseases

Neurotoxicity is a major health problem in Africa: focus on Parkinson's / Parkinsonism

ALPHA-SYNUCLEIN PHOSPHORYLATION DIRECTS TRAFFICKING OF THE V-SNARE SYNAPTOBREVIN-2

INFLAMMATORY STRESS SIGNALING ASSOCIATED WITH Α-SYNUCLEIN BURDEN IN CELLULAR MODELS OF PARKINSON’S DISEASE

UNRAVELING THE CONSEQUENCES OF INDUCED SYNUCLEINOPATHY IN DOPAMINERGIC AND NORADRENERGIC NEURONS

DIMETHYL FUMARATE MITIGATES ALPHA-SYNUCLEIN–INDUCED DEFECTS IN HUMAN 3D CORTICAL ORGANOIDS AND MOUSE MODELS OF SYNUCLEOPATHY

FROM SPIDER VENOM TO NOVEL INHIBITORS OF AΒ AND Α-SYNUCLEIN AGGREGATION

DIMETHYL FUMARATE REPURPOSING AGAINST ALPHA-SYNUCLEIN-INDUCED TOXICITY IN MICE

ALPHA-SYNUCLEIN DYNAMICS IN REACTIVE ASTROCYTES

INVESTIGATING SENESCENCE PHENOTYPES IN ASTROCYTES DERIVED FROM A53T Α-SYNUCLEIN PD-PATIENT IPSCS

DISSECTING THE INTERACTION BETWEEN THE ABERRANT PHASE SEPARATION OF ALPHA-SYNUCLEIN AND ORGANELLE MISLOCALIZATION

OBESITY AND AGING AS RISK FACTORS FOR LIPID DROPLET ACCUMULATION AND Α-SYNUCLEIN PATHOLOGY IN PARKINSON’S DISEASE

ALPHA-SYNUCLEIN DETECTION IN SKIN SAMPLES BY SEED AMPLIFICATION ASSAY FOR PARKINSON’S DISEASE DIAGNOSIS IN CHILEAN PATIENTS

EARLY Α-SYNUCLEIN PATHOLOGY IN MICE LEADS TO MOTOR DYSFUNCTION, DIFFERENTIAL MICROGLIA CLUSTERS AND ALTERED IMMUNE SIGNALING

INTRANASAL DELIVERY OF HELICURE REDUCES Α-SYNUCLEIN OLIGOMERS, ALTERS AUTOPHAGY MECHANISMS, AND RESCUES MOTOR DEFICITS IN A PARKINSON’S DISEASE MOUSE MODEL

GENERATING A NOVEL DOUBLE TRANSGENIC MOUSE MODEL FOR SELECTIVE ABLATION OF ALPHA-SYNUCLEIN IN THE BRAIN

PD MODEL USING IPSC-DERIVED AGED ASTROCYTES REVEALS INDUCTION OF NEUROTOXICITY BY STIMULATION WITH Α-SYNUCLEIN AND IFN-Γ

EARLY Α-SYNUCLEIN PATHOLOGY IN THE LOCUS COERULEUS DISRUPTS NORADRENERGIC CIRCUITS AND HIPPOCAMPAL FUNCTION IN A PRODROMAL PARKINSON’S DISEASE MODEL

LRRK2 INHIBITION INCREASES UPTAKE OF ALPHA-SYNUCLEIN FIBRILS IN HUMAN IPSC-DERIVED MICROGLIA​

THE A53T MUTATION IN Α-SYNUCLEIN ENHANCES PROINFLAMMATORY ACTIVATION IN HUMAN MICROGLIA UPON INFLAMMATORY STIMULUS

EARLY BLOOD–BRAIN BARRIER DYSFUNCTION AND CENTRAL-TO-PERIPHERAL Α-SYNUCLEIN SPREAD IN EXPERIMENTAL PARKINSON’S DISEASE

TARGETED DEGRADATION OF ΑLPHA-SYNUCLEIN LIMITS PATHOLOGICAL AGGREGATION IN A CELLULAR MODEL OF PARKINSON’S DISEASE

LATENT-TRAJECTORY MODELING OF LONGITUDINAL EEG ALTERATIONS IN PRODROMAL Α-SYNUCLEINOPATHIES

GBA1 L444P MUTATION INCREASES VULNERABILITY TO Α-SYNUCLEIN PATHOLOGY IN PRIMARY NEURONS

Α-SYNUCLEIN OLIGOMERS INDUCE MITOCHONDRIAL DYSFUNCTION AND TRIGGER EXTRACELLULAR MITOCHONDRIAL RELEASE: IMPLICATIONS FOR ASTROCYTE-NEURON CROSSTALK

THYMOQUINONE PREVENTS DOPAMINERGIC NEURONAL LOSS IN ΑLPHA-SYNUCLEIN PFF INDUCED MOUSE MODEL OF PARKINSON’S DISEASE

NLRP3 FACILITATES Α-SYNUCLEIN-INDUCED NIGRAL DOPAMINERGIC NEURONAL SENESCENCE THROUGH SATB1/DNA DAMAGE/P21 SIGNALING PATHWAY

ALPHA-SYNUCLEIN EFFECTS IN GBA PARKINSON’S MODEL: EARLY STRIATAL CIRCUIT REMODELING

NOVEL RECEPTORS FOR ALPHA SYNUCLEIN AGGREGATES: IMPLICATIONS IN PARKINSON DISEASE PATHOLOGY

INHIBITORS OF ALPHA-SYNUCLEIN AGGREGATION AND ER STRESS SUPPRESS NEURODEGENERATION IN PARKINSON’S DISEASE ORGANOID MODEL

EARLY NEUROINFLAMMATION DRIVES COGNITIVE AND SYNAPTIC IMPAIRMENTS IN Α-SYNUCLEIN PARKINSON’S DISEASE: THERAPEUTIC RESCUE BY IL-1Β BLOCKADE

POLYSTYRENE NANOPLASTICS AS MODULATORS OF ALPHA-SYNUCLEIN ACCUMULATION IN PARKINSON’S DISEASE MODELS

SEROTONERGIC Α-SYNUCLEINOPATHY DISRUPTS VMPFC–RAPHE CIRCUIT ACTIVITY AND CONNECTIVITY, PROMOTING AN ANXIETY-LIKE PHENOTYPE IN FEMALE MICE

Α-SYNUCLEIN ACCUMULATION IN THE MEDIAL PREFRONTAL CORTEX DRIVES ANXIETY-LIKE, COGNITIVE DEFICITS, AND SYNAPTIC REMODELING IN A MOUSE MODEL OF PARKINSON’S DISEASE

Saposin C reduces levels of α-synuclein and dislodges it from glucosylceramide-enriched lipid membranes

Role of TGF-beta signalling pathway against alpha synuclein-induced toxicity in a Parkinson’s disease cell model

Host to graft propagation of alpha-synuclein in Parkinson’s disease: intra-nigral versus intra-striatal transplantation

The role of microvascular changes during development and progression of Parkinson’s Disease in a human alpha-synuclein overexpression mouse model (line 61)

The role of EEF1A proteins at synapses and in synucleinopathy

Glycation of alpha-synuclein modulates aggregation and Parkinson’s disease-like phenotypes

Sex differences in behavioral phenotype and markers of the unfolded protein response (UPR) pathway in a mouse model overexpressing human α-synuclein

The role of activity-dependent phosphorylation in the presynaptic function of α-synuclein

LRRK2 INHIBITION INCREASES UPTAKE OF ALPHA-SYNUCLEIN FIBRILS IN HUMAN IPSC-DERIVED MICROGLIA