Razan Sheta

Modeling Parkinson’s pathology in human iPSC dopaminergic neurons uncovers key mechanisms of Lewy body formation and heterogeneity

Anne‐Laure Mahul‐Mellier, Lukas van den Heuvel, Maxime Teixeira, Manel Boussouf et autres

The aggregation of alpha-synuclein (aSyn) into intraneuronal inclusions of heterogeneous morphology, known as Lewy bodies (LBs), is a defining hallmark of Parkinson's disease (PD); yet, our understanding of the mechanisms underpinning their formation and heterogeneity remains incomplete. Here, we present a human …

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The emerging role of polo-like kinase 2 in Alzheimer's disease

Laura Martínez-Drudis, Razan Sheta, Dylan Musiol, Maxime Teixeira et autres

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by the accumulation of amyloid-β (Aβ) plaques and hyperphosphorylated Tau tangles. Protein phosphorylation is increasingly recognized as a key modulator of AD pathology, but the specific kinases involved remain incompletely characterized. Polo-like kinase …

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WDR44 drives de novo α-synuclein aggregation at the lysosomal membrane and promotes neuronal dysfunction in Parkinson’s Disease

Maxime Teixeira, Razan Sheta, Morgan Bérard, Christine Insinna et autres

. Despite significant advances in understanding α-SYN self-assembly, the precise sequence of early aggregation steps has not been directly visualized in living neurons. Here, we use an optogenetic-induced protein aggregation system with a high temporal resolution to monitor the onset of α-SYN …

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Optogenetic-induced α-synuclein accumulation reveals early synaptic dysfunction in experimental models of Parkinson’s disease

Raquel Rodríguez-Aller, Beatriz Romero-Quineche, Marc Morissette, Razan Sheta et autres

Presynaptic accumulation of misfolded α-synuclein (α-syn) and altered synaptic transmission are considered early events in the pathogenesis of Parkinson's disease (PD), suggesting a potential causal link between these two events. However, the mechanisms by which α-syn aggregation induces synaptic dysfunction and the …

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Interplay between lipid droplets and alpha-synuclein: implication in Parkinson’s disease pathogenesis

Walid Idi, Razan Sheta, Abid Oueslati

Lipid droplets (LDs), once considered inert lipid stores, are now recognized as active regulators of lipid metabolism, stress responses, and protein quality control in the brain. Their dysregulation is increasingly linked to neurodegenerative diseases, notably Parkinson's disease (PD). This review explores the …

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Recapitulating Parkinson’s pathology in human iPSC dopaminergic neurons reveals new mechanistic insights into Lewy body formation and heterogeneity

Anne‐Laure Mahul‐Mellier, Lukas van den Heuvel, Maxime Teixeira, Manel Boussouf et autres

Abstract The accumulation of alpha-synuclein (aSyn) into intraneuronal inclusions of heterogeneous morphology, known as Lewy bodies (LB), is one of the defining diagnostic features of Parkinson’s disease (PD); yet, our understanding of the mechanisms underpinning their formation and heterogeneity remains incomplete. Here, …

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Targeting ion channels in Parkinson’s disease: Insights from iPSC-derived dopaminergic neurons

Nour-elhouda Neili, Razan Sheta, Abid Oueslati, Ines ELBini

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Combining light-induced aggregation and biotin proximity labeling implicates endolysosomal proteins in early α-synuclein oligomerization

Maxime Teixeira, Razan Sheta, Dylan Musiol, Vetso Ranjakasoa et autres

Alpha-synuclein (α-syn) aggregation is a defining feature of Parkinson's disease (PD) and related synucleinopathies. Despite significant research efforts focused on understanding α-syn aggregation mechanisms, the early stages of this process remain elusive, largely due to limitations in experimental tools that lack the …

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Behavioral analysis of motor and non-motor impairment in rodent models of Parkinson's disease

Razan Sheta, Morgan Bérard, Dylan Musiol, Laura Martínez-Drudis et autres

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the degeneration of dopamine neurons in the substantia nigra pars compacta, leading to motor and non-motor symptoms. While motor symptoms such as rigidity, tremor, bradykinesia/akinesia, and postural instability are well-recognized, non-motor symptoms …

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The combination of optogenetic-induced protein aggregation and proximity biotinylation assays strongly implicates endolysosomal proteins in the early stages of α-synuclein aggregation

Maxime Teixeira, Razan Sheta, Dylan Musiol, Vetso Ranjakasoa et autres

Summary Alpha-synuclein (α-syn) aggregation is a defining feature of Parkinson’s disease (PD) and related synucleinopathies. Despite significant research efforts focused on understanding α-syn aggregation mechanisms, the early stages of this process remain elusive, largely due to limitations in experimental tools that lack …

ca (code pays fourni par la source)

Non-invasive systemic viral delivery of human alpha-synuclein mimics selective and progressive neuropathology of Parkinson’s disease in rodent brains

Morgan Bérard, Laura Martínez-Drudis, Razan Sheta, Omar M. A. El‐Agnaf et autres

BACKGROUND: Alpha-synuclein (α-syn) aggregation into proteinaceous intraneuronal inclusions, called Lewy bodies (LBs), is the neuropathological hallmark of Parkinson's disease (PD) and related synucleinopathies. However, the exact role of α-syn inclusions in PD pathogenesis remains elusive. This lack of knowledge is mainly due …

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Optogenetic-mediated induction and monitoring of α-synuclein aggregation in cellular models of Parkinson’s disease

Maxime Teixeira, Razan Sheta, Walid Idi, Abid Oueslati

Studying Parkinson’s disease (PD) is complex due to a lack of cellular models mimicking key aspects of protein pathology. Here, we present a protocol for inducing and monitoring α-synuclein aggregation in living cells using optogenetics. We describe steps for plasmid transduction, biochemical …

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