A5000174219- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Lysosomal Storage Disorders Research
- RNA regulation and disease
- Supramolecular Self-Assembly in Materials
- Glycogen Storage Diseases and Myoclonus
- Autophagy in Disease and Therapy
- Nerve injury and regeneration
University of Copenhagen
2020-2024
Alzheimer's disease (AD) is the most common cause of dementia, with no current cure. Consequently, alternative approaches focusing on early pathological events in specific neuronal populations, besides targeting well-studied amyloid beta (Aβ) accumulations and Tau tangles, are needed. In this study, we have investigated phenotypes to glutamatergic forebrain neurons mapped timeline their occurrence, by implementing familial sporadic human induced pluripotent stem cell models as well 5xFAD...
Intraneuronal accumulation of aggregated α-synuclein is a pathological hallmark Parkinson's disease. Therefore, mechanisms capable promoting deposition bear important pathogenetic implications. Mutations the glucocerebrosidase 1 (GBA) gene represent prevalent disease risk factor. They are associated with loss activity key enzyme involved in lipid metabolism, glucocerebrosidase, supporting mechanistic relationship between abnormal α-synuclein-lipid interactions and development Parkinson...
The presence of amyloid fibrils is a hallmark several neurodegenerative diseases. Some amyloidogenic proteins, such as α-synuclein and β, interact with lipids, this interaction can strongly favour the formation fibrils. In particular primary nucleation step,
Mutations in the gene GBA, encoding glucocerebrosidase (GCase), are highest genetic risk factor for Parkinson's disease (PD). GCase is a lysosomal glycoprotein responsible hydrolysis of glucosylceramide into glucose and ceramide. GBA cause decrease activity, stability protein levels which turn lead to accumulation lipid substrates as well α-synuclein (αS) vitro vivo. αS main constituent Lewy bodies found brain PD patients an increase its was be associated with activity/protein In this...
ABSTRACT Alzheimer’s disease (AD) is the most common cause of dementia, with no current cure. Consequently, alternative approaches focusing on early pathological events in specific neuronal populations, besides targeting well-studied Amyloid beta (Aβ) accumulations and Tau tangles, are needed. In this study, we have investigated phenotypes to glutamatergic forebrain neurons mapped timeline their occurrence, by implementing familial sporadic human induced pluripotent stem cell models as well...
The presence of amyloid fibrils is a hallmark several neurodegenerative diseases. Some amyloidogenic proteins, such as α-synuclein and β, can interact with lipids, this interaction strongly favor the formation fibrils. In particular primary nucleation step, i.e. de novo fibrils, has been shown to be accelerated by lipids. However, exact mechanism acceleration still mostly unclear. Here we use range scattering methods, dynamic light (DLS) small angle X-ray neutron (SAXS SANS) obtain...
Parkinson's Disease (PD) is characterised by the loss of dopaminergic neurons and deposition protein inclusions called Lewy Bodies (LBs). LBs are heterogeneous structures composed lipid molecules their main constituent presynaptic α-synuclein. SH-SY5Y cells neuroblastoma commonly used to model PD because they express markers α-synuclein can be differentiated into neuronal using established protocols. Despite increasing evidence pointing towards a role lipids in PD, limited knowledge...
Abstract Parkinson’s Disease (PD) is a neurodegenerative disorder characterised by the deposition of protein inclusions, called Lewy Bodies (LBs), in neurons. LBs are heterogeneous structures whose main constituent alpha-synuclein (αS) and that also composed lipid molecules. Disruptions levels specific lipids, including sphingolipids, fatty acids, cholesterol, have been associated with PD, suggesting role lipids emergence spreading αS PD pathology. Using combination shotgun lipidomics...
Abstract Parkinson’s Disease (PD) is characterized by the loss of dopaminergic neurons and deposition in remaining cells protein inclusions called Lewy Bodies (LBs). LBs are heterogeneous structures composed lipid molecules their main constituent presynaptic α-synuclein. SH-SY5Y neuroblastoma commonly used to model PD because they express markers α-synuclein can be differentiated into neuronal using established protocols. Despite increasing evidence pointing towards a role lipids initiation...