A5062998368- Neurogenetic and Muscular Disorders Research
- Amyotrophic Lateral Sclerosis Research
- RNA Research and Splicing
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic Neurodegenerative Diseases
- RNA modifications and cancer
- Immune Response and Inflammation
- Ubiquitin and proteasome pathways
- Immune cells in cancer
- Autophagy in Disease and Therapy
Macquarie University
2021-2024
Insoluble cytoplasmic aggregate formation of the RNA-binding protein TDP-43 is a major hallmark neurodegenerative diseases including Amyotrophic Lateral Sclerosis. localizes predominantly in nucleus, arranging itself into dynamic condensates through liquid-liquid phase separation (LLPS). Mutations and post-translational modifications can alter condensation properties TDP-43, contributing to transition liquid-like biomolecular solid-like aggregates. However, date it has been challenge study...
Abstract Amyotrophic lateral sclerosis (ALS)- and frontotemporal dementia (FTD)-linked mutations in CCNF have been shown to cause dysregulation protein homeostasis. encodes for cyclin F, which is part of the F-E3 ligase complex SCF cyclinF known ubiquitylate substrates proteasomal degradation. In this study, we identified a function F regulate substrate solubility show how mechanistically underlies ALS FTD disease pathogenesis. We demonstrated that FTD-associated sequestosome-1/p62 (p62) was...
Abstract Amyotrophic lateral sclerosis (ALS) is a form of motor neuron disease (MND) that characterized by the progressive loss neurons within spinal cord, brainstem, and cortex. Although ALS clinically manifests as heterogeneous disease, with varying onset survival, unifying feature presence ubiquitinated cytoplasmic protein inclusion aggregates containing TDP-43. However, precise mechanisms linking inclusions aggregation to neuronal are currently poorly understood. Bimolecular fluorescence...
SUMMARY TDP-43 is a nuclear RNA-binding protein that can undergo liquid-liquid phase separation (LLPS) and forms pathological insoluble aggregates in frontotemporal dementia amyotrophic lateral sclerosis (ALS). Perturbations of function are linked to mislocalization neurodegeneration. By studying vivo , we confirmed for the first time undergoes LLPS biomolecular condensates spinal motor neurons (MNs). Importantly, discovered interfering with K136 SUMOylation site altered its behavior,...
Abstract Amyotrophic lateral sclerosis (ALS) is a form of motor neuron disease (MND) that characterized by the progressive loss neurons within spinal cord, brainstem and cortex. Although ALS clinically manifests as heterogeneous disease, with varying onset survival, unifying feature presence ubiquitinated cytoplasmic protein inclusion aggregates containing TDP-43. However, precise mechanisms linking inclusions aggregation to neuronal are currently poorly understood. Bimolecular Fluorescence...