A5042674015- Parkinson's Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Lysosomal Storage Disorders Research
- Neurological diseases and metabolism
- Cellular transport and secretion
- Nuclear Receptors and Signaling
- Banana Cultivation and Research
- Peroxisome Proliferator-Activated Receptors
- Conducting polymers and applications
- RNA regulation and disease
- Botulinum Toxin and Related Neurological Disorders
- Nerve injury and regeneration
- Plant Gene Expression Analysis
- Coenzyme Q10 studies and effects
- RNA Research and Splicing
- Alzheimer's disease research and treatments
- NF-κB Signaling Pathways
University of Pittsburgh
2018-2024
Institute for Neurodegenerative Disorders
2018-2024
Wild-type LRRK2 is activated in nigrostriatal dopamine neurons idiopathic Parkinson’s disease and plays a pathogenic role this neurodegenerative disorder.
Alpha-synuclein (αS) is a conformationally plastic protein that reversibly binds to cellular membranes. It aggregates and genetically linked Parkinson's disease (PD). Here, we show αS directly modulates processing bodies (P-bodies), membraneless organelles function in mRNA turnover storage. The N terminus of αS, but not other synucleins, dictates mutually exclusive binding either membranes or P-bodies the cytosol. associates with multiple decapping proteins close proximity on Edc4 scaffold....
LRRK2 has been implicated in endolysosomal function and likely plays a central role idiopathic Parkinson's disease (iPD). In iPD, dopaminergic neurons within the substantia nigra are characterized by increased kinase activity, deficits, accumulation of autophagic vesicles with incompletely degraded substrates, including α-synuclein. Although function, it remains unclear whether inhibition activity can prevent deficits or reduce neurodegeneration. this study, we defects surviving iPD patient...
Abstract Individuals with Parkinson’s disease (PD) typically receive a diagnosis once they have developed motor symptoms, at which point there is already significant loss of substantia nigra dopamine neurons, α-synuclein accumulation in surviving and neuroinflammation. Consequently, the clinical presentation may be too late to initiate disease-modifying therapy. In contrast this reality, animal models often involve acute neurodegeneration potential therapies are tested concurrently or...
Mitochondrial dysfunction and oxidative stress are strongly implicated in Parkinson's disease (PD) pathogenesis there is evidence that mitochondrially-generated superoxide can activate NADPH oxidase 2 (NOX2). Although NOX2 has been examined the context of PD, most attention focused on glial NOX2, role neuronal PD remains to be defined. Additionally, pharmacological inhibitors have typically lacked specificity. Here we devised validated a proximity ligation assay for activity demonstrated...
Oxidative stress has long been implicated in Parkinson’s disease (PD) pathogenesis, although the sources and regulation of reactive oxygen species (ROS) production are poorly defined. Pathogenic mutations gene encoding leucine-rich repeat kinase 2 (LRRK2) associated with increased activity a greater risk PD. The substrates downstream consequences elevated LRRK2 still being elucidated, but overexpression mutant oxidative stress, antioxidants reportedly mitigate toxicity. Here, using...
Abstract To date there are no therapeutic strategies that limit the progression of Parkinson’s disease (PD). The mechanisms underlying PD-related nigrostriatal neurodegeneration remain incompletely understood, with multiple factors modulating course PD pathogenesis. This includes Nrf2-dependent gene expression, oxidative stress, α-synuclein pathology, mitochondrial dysfunction, and neuroinflammation. In vitro sub-acute in vivo rotenone rat models were used to evaluate neuroprotective...
Missense mutations in leucine rich-repeat kinase 2 (LRRK2) cause forms of familial Parkinson's disease and have been linked to 'idiopathic' disease. Assessment LRRK2 activity has very challenging due its size, complex structure, relatively low abundance. A standard the field assess is measure level substrate phosphorylation (pThr73-Rab10) or autophosphorylation serine 1292 (i.e., phosphoserine 1292; pS1292). The levels pS1292 typically assessed by western blotting, which limits cellular...
Mutations in
Abstract BACKGROUND: Individuals with Parkinson’s disease (PD) typically receive a diagnosis once they have developed motor symptoms, at which point there is already significant loss of substantia nigra dopamine neurons, α-synuclein accumulation in surviving and neuroinflammation. Consequently, the clinical presentation may be too late to initiate disease-modifying therapy. In contrast this reality, animal models often involve acute neurodegeneration potential therapies are tested...
Abstract To date there are no therapeutic strategies that limit the progression of Parkinson’s disease (PD). The mechanisms underlying PD-related nigrostriatal neurodegeneration remain incompletely understood, with multiple factors modulating course PD pathogenesis. This includes Nrf2-dependent gene expression, oxidative stress, α-synuclein pathology, mitochondrial dysfunction, and neuroinflammation. In vitro sub-acute in vivo rotenone rat models were used to evaluate neuroprotective...
Abstract Mitochondrial dysfunction and oxidative stress are strongly implicated in the pathogenesis of Parkinson’s disease (PD) there is evidence that mitochondrially-generated superoxide can activate NADPH oxidase 2 (NOX2), which a major enzymatic generator superoxide. Although NOX2 has been examined context PD, previous studies have focused on microglial function; role neuronal PD remains to be defined. Here we devised validated proximity ligation assay for activity demonstrated human...