A5004169353- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- Cellular transport and secretion
- Neurological disorders and treatments
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Nerve injury and regeneration
- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Lipid Membrane Structure and Behavior
- Genetic Neurodegenerative Diseases
- Functional Brain Connectivity Studies
- Ion channel regulation and function
- Neuroinflammation and Neurodegeneration Mechanisms
- Diet and metabolism studies
- Metabolism and Genetic Disorders
- Photoreceptor and optogenetics research
- Endoplasmic Reticulum Stress and Disease
- Neuroscience and Neural Engineering
- Neural dynamics and brain function
- Pancreatic function and diabetes
- Neurogenesis and neuroplasticity mechanisms
- Nicotinic Acetylcholine Receptors Study
- melanin and skin pigmentation
- Folate and B Vitamins Research
Columbia University Irving Medical Center
2016-2025
New York Psychoanalytic Society and Institute
2016-2025
New York State Psychiatric Institute
2016-2025
Columbia University
2014-2024
Research Foundation For Mental Hygiene
2021-2023
Neurology, Inc
2014
Sulzer (United States)
2006
University of Nebraska–Lincoln
2000-2003
National Medical Research Center for Hematology
1998
Altered degradation of α-synuclein (α-syn) has been implicated in the pathogenesis Parkinson disease (PD). We have shown that α-syn can be degraded via chaperone-mediated autophagy (CMA), a selective lysosomal mechanism for cytosolic proteins. Pathogenic mutants block translocation, impairing their own along with other CMA substrates. While pathogenic mutations are rare, undergoes posttranslational modifications, which may underlie its accumulation aggregates most forms PD. Using mouse...
Significance Successful completion of daily activities relies on the ability to select relevant features environment pay attention and remember. Disruptions these processes can lead disorders, such as attention-deficit hyperactivity disorder age-related memory loss. To devise therapeutic strategies, we must understand neural circuits underlying normal cognition. One important pathway is signaling dopamine, a reinforcement-related neurotransmitter, in hippocampus, spatial learning center....
Homocysteine is a key junction metabolite in methionine metabolism. It suffers two major metabolic fates: transmethylation catalyzed by synthase or betaine homocysteine methyl transferase and transsulfuration cystathionine β-synthase leading to cystathionine. The latter subsequently converted cysteine, precursor of glutathione. Studies with purified mammalian have revealed the oxidative sensitivity both enzymes, suggesting hypothesis that redox regulation this pathway may be physiologically...
α-Synuclein (α-syn), a protein implicated in Parkinson's disease pathogenesis, is presynaptic suggested to regulate transmitter release. We explored how α-syn overexpression PC12 and chromaffin cells, which exhibit low endogenous levels relative neurons, affects catecholamine Overexpression of wild-type or A30P mutant cell lines inhibited evoked release without altering calcium threshold cooperativity Electron micrographs revealed that vesicular pools were not reduced but that, on the...
Parkinson's disease (PD) has been attributed to a combination of genetic and nongenetic factors. We studied set monozygotic twins harboring the heterozygous glucocerebrosidase mutation (GBA N370S) but clinically discordant for PD. applied induced pluripotent stem cell (iPSC) technology PD modeling using twins' fibroblasts evaluate dissect contributions. Utilizing fluorescence-activated sorting, we obtained homogenous population "footprint-free" iPSC-derived midbrain dopaminergic (mDA)...
Parkinson's disease (PD) is characterized by the selective loss of dopamine neurons in substantia nigra; however, mechanism neurodegeneration PD remains unclear. A subset familial linked to mutations PARK2 and PINK1, which lead dysfunctional mitochondria-related proteins Parkin suggesting that pathways implicated these monogenic forms could play a more general role PD. We demonstrate identification disease-related phenotypes PD-patient-specific induced pluripotent stem cell (iPSC)-derived...
Abstract In Parkinson’s disease and other synucleinopathies, the elevation of α-synuclein phosphorylated at Serine129 (pS129) is a widely cited marker pathology. However, physiological role for pS129 has remained undefined. Here we use multiple approaches to show first time that functions as regulator neuronal activity. Neuronal activity triggers sustained increase in cultured neurons (200% within 4 h). accord, brain elevated environmentally enriched mice exhibiting enhanced long-term...
The nervous system transmits signals between neurons via neurotransmitter release during synaptic vesicle fusion. In order to observe uptake and from individual presynaptic terminals directly, we designed fluorescent false neurotransmitters as substrates for the monoamine transporter. Using these probes image dopamine in striatum, made several observations pertinent plasticity. We found that fraction of vesicles releasing per stimulus was dependent on frequency. A kinetically distinct...
Dysregulation of dopamine homeostasis and elevation the cytosolic level transmitter have been suggested to underlie vulnerability catecholaminergic neurons in Parkinson’s disease. Because several known mutations α-synuclein or overexpression wild-type (WT) protein causes familial forms disease, we investigated possible links between pathogenesis homeostasis. Chromaffin cells isolated from transgenic mice that overexpress A30P displayed significantly increased catecholamine levels as measured...
Epithelial-neuronal signaling is essential for sensory encoding in touch, itch, and nociception; however, little known about the release mechanisms neurotransmitter receptors through which skin cells govern neuronal excitability. Merkel are mechanosensory epidermal that have long been proposed to activate afferents chemical synaptic transmission. We employed a set of classical criteria neurotransmission as framework test this hypothesis. RNA sequencing adult mouse demonstrated they express...
Abstract Amphetamines elevate extracellular dopamine, but the underlying mechanisms remain uncertain. Here we show in rodents that acute pharmacological inhibition of vesicular monoamine transporter (VMAT) blocks amphetamine-induced locomotion and self-administration without impacting cocaine-induced behaviours. To study VMAT’s role mediating amphetamine action dopamine neurons, have used novel genetic, optical approaches Drosophila melanogaster . In an ex vivo whole-brain preparation,...
Significance Ca 2+ homeostasis is indispensable for the well being of all living organisms. disrupted by α-synuclein (α-syn), whose misfolding plays a major role in neurodegenerative diseases termed synucleinopathies, such as Parkinson disease. We report that α-syn can induce sustained and highly elevated levels cytoplasmic , thereby activating calcineurin (CN) cascade results toxicity. CN conserved –calmodulin (CaM)-dependent phosphatase critical sensing concentrations transducing...