A5026787858- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological disorders and treatments
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Nuclear Receptors and Signaling
- Nerve injury and regeneration
- Neural dynamics and brain function
- Neuroscience and Neural Engineering
- Genetic Neurodegenerative Diseases
- Photoreceptor and optogenetics research
- Ion channel regulation and function
- Mitochondrial Function and Pathology
- RNA regulation and disease
- Lysosomal Storage Disorders Research
- Photochromic and Fluorescence Chemistry
- Endoplasmic Reticulum Stress and Disease
- CAR-T cell therapy research
- Neurological diseases and metabolism
- Neurogenesis and neuroplasticity mechanisms
- T-cell and B-cell Immunology
- Genetics and Neurodevelopmental Disorders
Columbia University Irving Medical Center
2016-2025
New York State Psychiatric Institute
2016-2025
Columbia University
2016-2025
New York Psychoanalytic Society and Institute
2016-2025
Research Network (United States)
2021-2025
La Jolla Institute for Immunology
2024
Research Foundation For Mental Hygiene
2018-2023
Karlsruhe Institute of Technology
2021
Columbia College
2020
Royal College of Physicians
2020
Aberrant alpha-synuclein degradation is implicated in Parkinson's disease pathogenesis because the protein accumulates Lewy inclusion bodies associated with disease. Little known, however, about pathways by which wild-type normally degraded. We found that was selectively translocated into lysosomes for chaperone-mediated autophagy pathway. The pathogenic A53T and A30P mutants bound to receptor this pathway on lysosomal membrane, but appeared act as uptake blockers, inhibiting both their own...
Whether amphetamine acts principally at the plasma membrane or synaptic vesicles is controversial. We find that d-amphetamine injection into Planorbis giant dopamine neuron causes robust release, demonstrating specific uptake not required. Arguing for action vesicles, whole-cell capillary electrophoresis of single neurons shows reduces vesicular dopamine, while quantal release from PC12 cells by > 50% per vesicle. Intracellular produces rapid nomifensine-sensitive showing an increased...
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....
Parkinson's disease (PD) is most commonly a sporadic illness, and characterized by degeneration of substantia nigra dopamine (DA) neurons abnormal cytoplasmic aggregates α-synuclein. Rarely, PD may be caused missense mutations in MPTP, neurotoxin that inhibits mitochondrial complex I, prototype for an environmental cause because it produces pattern DA neurodegeneration closely resembles the neuropathology PD. Here we show α-synuclein null mice display striking resistance to MPTP-induced...
Alpha-synuclein mutations have been identified in certain families with Parkinson's disease (PD), and alpha-synuclein is a major component of Lewy bodies. Other genetic data indicate that the ubiquitin-dependent proteolytic system involved PD pathogenesis. We generated stable PC12 cell lines expressing wild-type or A53T mutant human alpha-synuclein. Lines but not show: (1) disruption system, manifested by small cytoplasmic ubiquitinated aggregates an increase polyubiquitinated proteins; (2)...
Quantal release of the principal excitatory neurotransmitter glutamate requires a mechanism for its transport into secretory vesicles. Within brain, complementary expression vesicular transporters (VGLUTs) 1 and 2 accounts by all known neurons. We now report identification VGLUT3 many cells generally considered to classical transmitter with properties very different from glutamate. Remarkably, subpopulations inhibitory neurons as well cholinergic interneurons, monoamine neurons, glia express...
Methamphetamine (MA) produces selective degeneration of dopamine (DA) neuron terminals without cell body loss. While excitatory amino acids (EAAs) contribute to MA toxicity, terminal loss is not characteristic excitotoxic lesions nor excitotoxicity for DA fibers; rather, EAAs may modulate MA-induced turnover, suggesting that DA-dependent events play a key role in neurotoxicity. To examine this possibility, we used postnatal ventral midbrain cultures maintained under continuous EAA blockade....
Melanin, the pigment in hair, skin, eyes, and feathers, protects external tissue from damage by UV light. In contrast, neuromelanin (NM) is found deep brain regions, specifically loci that degenerate Parkinson's disease. Although this distribution suggests a role for NM disease neurodegeneration, biosynthesis function of have eluded characterization because lack an experimental system. We induced rat substantia nigra PC12 cell cultures exposure to l -dihydroxyphenylalanine, which rapidly...
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...
Dopamine (DA) transmission is governed by processes that regulate release from axonal boutons in the forebrain and somatodendritic compartment midbrain, clearance DA transporter, diffusion, extracellular metabolism. We review how regulated neuronal activity autoreceptors heteroreceptors, address quantal events are size frequency. In brain regions densely innervated axons, due predominantly to uptake whereas cortex, other with relatively sparse inputs, norepinephrine transporter diffusion...