A5000417123- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Alzheimer's disease research and treatments
- Autophagy in Disease and Therapy
- Nerve injury and regeneration
- Lysosomal Storage Disorders Research
- Nuclear Receptors and Signaling
- Mitochondrial Function and Pathology
- Neurological diseases and metabolism
- Botulinum Toxin and Related Neurological Disorders
- RNA Interference and Gene Delivery
- Genetic Neurodegenerative Diseases
- RNA regulation and disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- Virus-based gene therapy research
- Cellular transport and secretion
- CRISPR and Genetic Engineering
- Autism Spectrum Disorder Research
- Viral Infections and Immunology Research
- Trace Elements in Health
- Prion Diseases and Protein Misfolding
- Neuroscience and Neural Engineering
- Cannabis and Cannabinoid Research
Centre National de la Recherche Scientifique
2016-2025
Université de Bordeaux
2016-2025
Institut des Maladies Neurodégénératives
2015-2024
Donostia International Physics Center
2024
University of the Basque Country
2024
Biomedical Research Networking Center on Neurodegenerative Diseases
2010-2024
Université Grenoble Alpes
2024
Basque Center for Materials, Applications and Nanostructures
2024
Ikerbasque
2024
Achucarro Basque Center for Neuroscience
2024
Mounting evidence suggests a role for autophagy dysregulation in Parkinson's disease (PD). The bulk degradation of cytoplasmic proteins (including α-synuclein) and organelles (such as mitochondria) is mediated by macroautophagy, which involves the sequestration cytosolic components into autophagosomes (AP) its delivery to lysosomes. Accumulation AP occurs postmortem brain samples from PD patients, has been widely attributed an induction autophagy. However, cause pathogenic significance these...
Mounting evidence suggests that α-synuclein, a major protein component of Lewy bodies (LB), may be responsible for initiating and spreading the pathological process in Parkinson disease (PD). Supporting this concept, intracerebral inoculation synthetic recombinant α-synuclein fibrils can trigger pathology mice. However, it remains uncertain whether pathogenic effects apply to PD-linked occur species closer humans.Nigral LB-enriched fractions containing were purified from postmortem PD brains...
Parkinson disease (PD) is a progressive neurodegenerative disorder pathologically characterized by the loss of dopaminergic neurons from substantia nigra pars compacta and presence, in affected brain regions, protein inclusions named Lewy bodies (LBs). The ATP13A2 gene (locus PARK9) encodes ATP13A2, lysosomal type 5 P-type ATPase that linked to autosomal recessive familial parkinsonism. physiological function hence its role PD, remains be elucidated. Here, we show PD-linked mutations lead...
Lysosomal impairment causes lysosomal storage disorders (LSD) and is involved in pathogenesis of neurodegenerative diseases, notably Parkinson disease (PD). Strategies enhancing or restoring lysosomal-mediated degradation thus appear as tantalizing disease-modifying therapeutics. Here we demonstrate that poly(DL-lactide-co-glycolide) (PLGA) acidic nanoparticles (aNP) restore impaired function a series toxin genetic cellular models PD, i.e. ATP13A2-mutant depleted cells glucocerebrosidase...
Abstract In Parkinson’s disease, synucleinopathy is hypothesized to spread from the enteric nervous system, via vagus nerve, CNS. Here, we compare, in baboon monkeys, pathological consequences of either intrastriatal or injection α-synuclein-containing Lewy body extracts patients with disease. This study shows that patient-derived α-synuclein aggregates are able induce nigrostriatal lesions and system pathology after striatal a non-human primate model. finding suggests progression might be...
Dysfunction of mitochondrial complex I is associated with a wide spectrum neurodegenerative disorders, including Parkinson's disease (PD). In rodents, inhibition leads to degeneration dopaminergic neurons the substantia nigra pars compacta (SNpc), as seen in PD, through activation mitochondria-dependent apoptotic molecular pathways. this scenario, blockade increases soluble pool cytochrome c intermembrane space oxidative mechanisms, whereas pro-cell death protein Bax actually necessary...
Human embryonic stem cells (hESC) and induced pluripotent (iPSC) offer great hope for in vitro modeling of Parkinson's disease (PD), as well designing cell-replacement therapies. To realize these opportunities, there is an urgent need to develop efficient protocols the directed differentiation hESC/iPSC into dopamine (DA) neurons with specific characteristics cell population lost PD, i.e., A9-subtype ventral midbrain DA neurons. Here we use lentiviral vectors drive expression LMX1A, which...
l-DOPA–induced dyskinesia (LID), a detrimental consequence of dopamine replacement therapy for Parkinson’s disease, is associated with an alteration in D1 receptor (D1R) and glutamate interactions. We hypothesized that the synaptic scaffolding protein PSD-95 plays pivotal role this process, as it interacts D1R, regulates its trafficking function, overexpressed LID. Here, we demonstrate rat macaque models disrupting interaction between D1R striatum reduces LID development severity. Single...
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons as well presence proteinaceous inclusions named Lewy bodies. α-synuclein (α-syn) major constituent bodies, and first disease-causing protein in PD. Several α-syn-based animal models PD have been developed to investigate pathophysiology PD, but none them recapitulate full picture disease. Ageing most compelling risk factor for developing its impact on α-syn toxicity remains...
Abstract In recent years, exploration of the brain extracellular space (ECS) has made remarkable progress, including nanoscopic characterizations. However, whether ECS precise conformation is altered during pathology remains unknown. Here we study nanoscale organization pathological in adult mice under degenerative conditions. Using electron microscopy cryofixed tissue and single nanotube tracking live slices combined with super-resolution imaging analysis, find enlarged dimensions increased...
Abstract Transportation of key proteins via extracellular vesicles has been recently implicated in various neurodegenerative disorders, including Parkinson’s disease, as a new mechanism disease spreading and source biomarkers. Extracellular likely to be derived from the brain can isolated peripheral blood have reported contain higher levels α-synuclein (α-syn) patients. However, very little is known about multiple system atrophy, that, like involves pathological α-syn aggregation, though...
Cytoplasmic alpha-synuclein (αSyn) aggregates are a typical feature of Parkinson's disease (PD). Extracellular insoluble αSyn can induce pathology in healthy neurons suggesting that PD neurodegeneration may spread through cell-to-cell transfer proteopathic seeds. Early pro-homeostatic reaction microglia to toxic forms remains elusive, which is especially relevant considering the recently uncovered microglial molecular diversity. Here, we show periventricular subependymal neurogenic niche...
Nine neurodegenerative diseases, such as Huntington, are caused by a polyglutamine (poly(Q)) expansion in otherwise unrelated proteins. Although poly(Q) causes aggregation of the affected proteins, protein context might determine selective neuronal vulnerability found each disease. Here we have report that, although expression Huntingtin derivatives with pathological innocuous yeast, deletion flanking proline-rich region alters shape and number inclusions unmasks toxic properties....
Lysosomal disruption is increasingly regarded as a major pathogenic event in Parkinson disease (PD). A reduced number of intraneuronal lysosomes, decreased levels lysosomal-associated proteins and accumulation undegraded autophagosomes (AP) are observed PD-derived samples, including fibroblasts, induced pluripotent stem cell-derived dopaminergic neurons, post-mortem brain tissue. Mechanistic studies toxic genetic rodent PD models attribute PD-related lysosomal breakdown to abnormal membrane...