A5071153942- Parkinson's Disease Mechanisms and Treatments
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Genetic Neurodegenerative Diseases
- Nuclear Receptors and Signaling
- Metabolism and Genetic Disorders
- Autophagy in Disease and Therapy
- Nerve injury and regeneration
- Alzheimer's disease research and treatments
- Endoplasmic Reticulum Stress and Disease
- Neurotransmitter Receptor Influence on Behavior
- Genetics and Neurodevelopmental Disorders
University of California, San Francisco
2020-2025
Gladstone Institutes
2020-2025
The University of Sydney
2024
Abstract Cell death is a critical process that occurs normally in health and disease. However, its study limited due to available technologies only detect very late stages the or specific mechanisms. Here, we report development of family fluorescent biosensors called genetically encoded indicators (GEDIs). GEDIs specifically an intracellular Ca 2+ level cells achieve early cell marks stage at which are irreversibly committed die. The time-resolved nature GEDI delineates binary demarcation...
Altered mitochondrial quality control and dynamics may contribute to neurodegenerative diseases, including Parkinson's disease, but we understand little about these processes in neurons. We combined time-lapse microscopy correlative light electron track individual mitochondria neurons lacking the fission-promoting protein dynamin-related 1 (Drp1) delineate kinetics of PINK1-dependent pathways control. Depolarized recruit Parkin outer membrane, triggering autophagosome formation, rapid...
Parkinson’s disease (PD) is characterized by the death of substantia nigra (SNc) dopamine (DA) neurons, but pathophysiological mechanisms that precede and drive their remain unknown. The activity DA neurons likely altered in PD, we understand little about if or how chronic changes may contribute to degeneration. To address this question, developed a chemogenetic (DREADD) mouse model chronically increase neuron activity, confirmed using ex vivo electrophysiology. Chronic hyperactivation...
Alterations in mitochondrial fission may contribute to the pathophysiology of several neurodegenerative diseases, including Alzheimer's disease (AD). However, we understand very little about normal functions or how disruption interact with AD-associated proteins modulate pathogenesis. Here show that loss central protein dynamin-related 1 (Drp1) CA1 and other forebrain neurons markedly worsens learning memory mice expressing mutant human amyloid precursor (hAPP) neurons. In cultured neurons,...
Mutations in the mitochondrial protein CHCHD2 cause autosomal dominant Parkinson's disease characterized by preferential loss of substantia nigra dopamine (DA) neurons. Therefore, understanding function neurons may provide vital insights into how dysfunction contributes to neurodegeneration PD. To investigate normal requirement and neurons, we first examined levels showed that DA have higher than other neuron types, both vivo co-culture. We then generated mice with either a targeted deletion...
Abstract Parkinson’s disease (PD) is characterized by the death of substantia nigra (SNc) dopamine (DA) neurons, but pathophysiological mechanisms that precede and drive their remain unknown. The activity DA neurons likely altered in PD, we understand little about if or how chronic changes may contribute to degeneration. To address this question, developed a chemogenetic (DREADD) mouse model chronically increase neuron activity, confirmed using ex vivo electrophysiology. Chronic...
Parkinson’s disease (PD) is characterized by the death of substantia nigra (SNc) dopamine (DA) neurons, but pathophysiological mechanisms that precede and drive their remain unknown. The activity DA neurons likely altered in PD, we understand little about if or how chronic changes may contribute to degeneration. To address this question, developed a chemogenetic (DREADD) mouse model chronically increase neuron activity, confirmed using ex vivo electrophysiology. Chronic hyperactivation...
Parkinson’s disease (PD) is characterized by the death of substantia nigra (SNc) dopamine (DA) neurons, but pathophysiological mechanisms that precede and drive their remain unknown. The activity DA neurons likely altered in PD, we understand little about if or how chronic changes may contribute to degeneration. To address this question, developed a chemogenetic (DREADD) mouse model chronically increase neuron activity, confirmed using ex vivo electrophysiology. Chronic hyperactivation...
Parkinson disease remains a debilitating neurodegenerative disorder, despite the discovery of multiple causative genes that account for familial forms. Prominent among these are PRKN/Parkin and PINK1, whose protein products participate in mitochondrial turnover, or mitophagy. But our poor understanding basic biological mechanisms driven by those neurons limits ability to target them therapeutically. Here, we summarize recent findings enabled new platform track individual mitochondria...
ABSTRACT Alterations in mitochondrial fission may contribute to the pathophysiology of several neurodegenerative diseases, including Alzheimer’s disease (AD). However, we understand very little about normal functions fission, or how disruption interact with AD-associated proteins modulate pathogenesis. Here show that loss central protein dynamin-related 1 (Drp1) CA1 and other forebrain neurons markedly worsens learning memory mice expressing mutant human amyloid-precursor (hAPP) neurons. In...