Publications related to Conditional expression of Parkinson's disease-related R1441C LRRK2 in midbrain dopaminergic neurons of mice causes nuclear abnormalities without neurodegeneration

Related publications (35)

A novel allosteric GCase modulator prevents Tau accumulation in GBA1WT and GBA1L444P/L444P cellular models

A slow decline in the autophagy-lysosomal pathway is a hallmark of the normal aging brain. Yet, an acceleration of this cellular function may propel neurodegenerative events. In fact, mutations in genes associated with the autophagy-lysosomal pathway can l ...

Springer Science and Business Media LLC2025

Control of nuclear envelope dynamics during acute ER stress by LINC complexes disassembly and selective, asymmetric autophagy of the outer nuclear membrane

Maurizio Molinari

The endoplasmic reticulum (ER) extends to the outer (ONM) and the inner (INM) nuclear membrane forming the nuclear envelope (NE) that delimits the nucleoplasm containing the cell genome. Unfolded protein responses (UPRs) and reticulophagy responses increas ...

Taylor & Francis Inc2024

Disentangling Multiple System Atrophy - Structural insights from alpha-synuclein fibrils and tissue pathology

Domenic Burger

Multiple System Atrophy (MSA) is an aggressive neurodegenerative disorder characterized by the formation of Glial Cytoplasmic Inclusions (GCI) containing alpha-synuclein (aSyn) fibrils in brain tissue. The fundamental causes for many neurodegenerative dise ...

EPFL2024

Distinct ultrastructural phenotypes of glial and neuronal alpha-synuclein inclusions in multiple system atrophy

Henning Paul-Julius Stahlberg, Marta Di Fabrizio, Amanda Jennifer Lewis, Domenic Burger

Multiple System Atrophy is characterized pathologically by the accumulation of alpha-synuclein (aSyn) into glial cytoplasmic inclusions (GCIs). The mechanism underlying the formation of GCIs is not well understood. In this study, correlative light and elec ...

2024

Striatal Dopamine Signals and Reward Learning

Meriam Malekzadeh, Robin François Virginien Dard, Carl Petersen, Sylvain Crochet, Yanqi Liu, Parviz Ghaderi, Christos Sourmpis, Pol Bech Vilaseca, Mauro Pulin, Anthony Pierre Robert Renard

We are constantly bombarded by sensory information and constantly making decisions on how to act. In order to optimally adapt behavior, we must judge which sequences of sensory inputs and actions lead to successful outcomes in specific circumstances. Neuro ...

Oxford Univ Press2023

Dynamics of CLIMP-63 S-acylation control ER morphology

Vassily Hatzimanikatis, Françoise Gisou van der Goot Grunberg, Graham Knott, Kathryn Hess Bellwald, Luciano Andres Abriata, Laurence Gouzi Abrami, Patrick Alain Sandoz, Catherine Maclachlan, Béatrice Kunz, Sylvia Ho, Gard Spreemann, Robin Alexander Denhardt-Eriksson

A key player in the formation of endoplasmic reticulum sheets is CLIMP-63, but mechanistic details remained elusive. Here authors combined cellular experiments and mathematical modelling to show that S-acylation of CLIMP-63 regulates its function by mediat ...

Nature Portfolio2023

Overexpression of human alpha-Synuclein leads to dysregulated microbiome/metabolites with ageing in a rat model of Parkinson disease

Joan Romani Aumedes, Hilal Lashuel, Yogesh Singh Chauhan, Florian Lang

Background Braak's hypothesis states that sporadic Parkinson's disease (PD) follows a specific progression of pathology from the peripheral to the central nervous system, and this progression can be monitored by detecting the accumulation of alpha-Synuclei ...

BMC2023

GABAergic-like dopamine synapses in the brain

Maria Reva

Dopamine synapses play a crucial role in volitional movement and reward-related behaviors, while dysfunction of dopamine synapses causes various psychiatric and neurological disorders. Despite this significance, the true biological nature of dopamine synap ...

2023

Plasticity of sensory representations in the posterior insular cortex during fear learning

Denys Osypenko

Aversively-motivated associative learning allows animals to avoid harm and thus ensures survival. Aversive learning can be studied by the fear learning paradigm, in which an innocuous sensory stimulus like a tone (conditioned stimulus, CS), acquires a nega ...

EPFL2023

Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson's Disease and Multiple System Atrophy

Hilal Lashuel, Melek Firat Altay

Aggregated alpha-synuclein (alpha-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA ...

MDPI2022

Olfactory modulation of barrel cortex activity during active whisking and passive whisker stimulation

Anthony Pierre Robert Renard

Rodents depend on olfaction and touch to meet many of their fundamental needs. However, the impact of simultaneous olfactory and tactile inputs on sensory representations in the cortex remains elusive. To study these interactions, we recorded large populat ...

Nature Portfolio2022

Exploring the mechanisms governing nuclear cGAS localization and activity

Marilena Wischnewski

Recognition of pathogen-derived molecules through germline-encoded receptors is a fundamental principle of innate immunity. Pattern recognition receptors detect specific intracellular danger signals to trigger potent immune responses. The DNA sensor cyclic ...

EPFL2022

Alpha-synuclein as a Potential Biomarker for Parkinson’s Disease and Other Synucleinopathies: Gaps, Challenges, and Opportunities

Hilal Lashuel, Pedro José Santana Ribeiro Magalhães

Parkinson's disease (PD), the second most common progressive neurodegenerative disease, develops and progresses for 10-15 years before the clinical diagnostic symptoms of the disease are manifested. Furthermore, several aspects of PD pathology overlap with ...

2022

Dopamine Dynamics in Reward-based Learning

Jun Huang

Dopamine signals are thought to be important for reward-based learning and appear to play important roles in regulating synaptic plasticity in the nucleus accumbens and the striatum. However, the precise neuronal circuit mechanisms underlying the learning ...

EPFL2022

Active microrheology in corrugated channels: Comparison of thermal and colloidal baths

Ignacio Pagonabarraga Mora

Hypothesis: The dynamics of colloidal suspension confined within porous materials strongly differs from that in the bulk. In particular, within porous materials, the presence of boundaries with complex shapes entangles the longitudinal and transverse degre ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2022

Glutathione in the nucleus accumbens regulates motivation to exert reward-incentivized effort

Maria del Carmen Sandi Perez, Lijing Xin, Olivia Zanoletti, João Pedro de Matos Rodrigues, Fiona Hollis, Pascal Steiner, Simone Astori, Ioannis Zalachoras, Alina Veronika Irene Strasser, Eva Ramos Fernandez

Emerging evidence is implicating mitochondrial function and metabolism in the nucleus accumbens in motivated performance. However, the brain is vulnerable to excessive oxidative insults resulting from neurometabolic processes, and whether antioxidant level ...

2022

Towards elucidating the structural and cellular determinants of a-synuclein seeding and toxicity

Somanath Jagannath

Although it has been nearly two and half decades since the discovery of alpha-synuclein (aSyn) as the major component of Lewy bodies (LBs), our understanding of the involvement of different aSyn species, their seeding, spreading and toxicity in Parkinson's ...

EPFL2022

Pde-Constrained Optimization For Nuclear Mechanics

Aleix Boquet I Pujadas

We propose an image based PDE-constrained optimisation framework to compute the dynamical quantities of a cell nucleus undergoing deformation. It allows retrieving the displacement, strain and stress at each pixel of the nuclear domain, as well as the trac ...

IEEE2022

N-terminal mutant huntingtin deposition correlates with CAG repeat length and symptom onset, but not neuronal loss in Huntington's disease

Hilal Lashuel, Nathan Alain Denis Riguet, Lorène Aeschbach

Huntington's disease (HD) is caused by a CAG repeat expansion mutation in the gene encoding the huntingtin (Htt) protein, with mutant Htt protein subsequently forming aggregates within the brain. Mutant Htt is a current target for novel therapeutic strateg ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2022

Opposite effects of stress on effortful motivation in high and low anxiety are mediated by CRHR1 in the VTA

Maria del Carmen Sandi Perez, Olivia Zanoletti, Simone Astori, Jocelin Grosse, Marie-Isabelle Guillot de Suduiraut, Ioannis Zalachoras

Individuals frequently differ in their behavioral and cognitive responses to stress. However, whether motivation is differently affected by acute stress in different individuals remains to be established. By exploiting natural variation in trait anxiety in ...

2022