A5091447772- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Autophagy in Disease and Therapy
- Parkinson's Disease Mechanisms and Treatments
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Biochemical Acid Research Studies
- Cardiomyopathy and Myosin Studies
- CRISPR and Genetic Engineering
- Prion Diseases and Protein Misfolding
- Neuroscience and Neural Engineering
- Pluripotent Stem Cells Research
- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Histone Deacetylase Inhibitors Research
- Neuroinflammation and Neurodegeneration Mechanisms
KU Leuven
2017-2023
VIB-KU Leuven Center for Brain & Disease Research
2018-2023
Vlaams Instituut voor Biotechnologie
2023
Leuven Institute for Fertility and Embryology
2018
A hexanucleotide repeat expansion in the C9orf72 gene is most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). How this mutation leads to these neurodegenerative diseases remains unclear. Here, we show using patient stem cell-derived motor neurons that impairs microtubule-based transport, a process critical for neuronal survival. Cargo transport defects are recapitulated by treating from healthy individuals with proline-arginine glycine-arginine...
TDP-43 is the major component of pathological inclusions in most ALS patients and up to 50% with frontotemporal dementia (FTD). Heterozygous missense mutations TARDBP, gene encoding TDP-43, are one common causes familial ALS. In this study, we investigate protein behavior induced pluripotent stem cell (iPSC)-derived motor neurons from three different TARDBP mutations, healthy controls an isogenic control. TARDPB induce several changes spinal neurons, including cytoplasmic mislocalization...
Abstract Energy metabolism has been repeatedly linked to amyotrophic lateral sclerosis (ALS). Yet, motor neuron (MN) remains poorly studied and it is unknown if ALS MNs differ metabolically from healthy MNs. To address this question, we first performed a metabolic characterization of induced pluripotent stem cells (iPSCs) versus iPSC-derived subsequently compared patients carrying FUS mutations their CRISPR/Cas9-corrected counterparts. We discovered that human iPSCs undergo lactate...
Abstract Introduction Tauopathies are neurodegenerative diseases characterized by TAU protein–related pathology, including frontotemporal dementia and Alzheimer's disease among others. Mutant animal models available, but none of them faithfully recapitulates human pathology not suitable for drug screening. Methods To create a new in vitro tauopathy model, we generated footprint‐free triple MAPT ‐mutant induced pluripotent stem cell line (N279K, P301L, E10+16 mutations) using clustered...
Abstract Background Motor neurons (MNs), which are primarily affected in amyotrophic lateral sclerosis (ALS), a specialized type of that long and non-dividing. Given their unique structure, these cells heavily rely on transport organelles along axons the process autophagy to maintain cellular homeostasis. It has been shown disruption pathway is sufficient cause progressive neurodegeneration defects have associated with various subtypes ALS, including those caused by hexanucleotide repeat...
TAR DNA binding protein 43 (TDP-43) is the main disease in most patients with amyotrophic lateral sclerosis (ALS) and about 50% of frontotemporal dementia (FTD). TDP-43 pathology not restricted to missense mutations TARDBP, gene encoding TDP-43, but also occurs ALS/FTD without known genetic cause or various other mutations. Mutations progranulin (GRN), which result a reduction ~ (PGRN) levels, FTD pathology. How loss PGRN leads whether expression protects against TDP-43-induced...
ABSTRACT Hexanucleotide repeat expansions in the C9orf72 gene are most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). How this mutation leads to these neurodegenerative diseases remains unclear. Here, we use human induced pluripotent stem cell-derived motor neurons show that impair microtubule-based transport mitochondria, a process critical for maintenance neuronal function. Cargo defects recapitulated by treating healthy with arginine-rich...
The past decades in Alzheimer's Disease (AD) research focused on the understanding of role amyloid beta and tau-protein aggregates pathophysiology AD. At least 30 mutations tau gene (MAPT) have been associated with familial forms frontotemporal dementia (FTD), shown to increase aggregation drive synaptic failure observed during disease progression. However, normal neuronal function still remains elusive has only studied set-ups low scalability limited translational value. As induced...