A5049248968- Parkinson's Disease Mechanisms and Treatments
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Alzheimer's disease research and treatments
- Genetics, Bioinformatics, and Biomedical Research
- Genetics and Neurodevelopmental Disorders
- Circadian rhythm and melatonin
- Nuclear Receptors and Signaling
- RNA regulation and disease
- Sleep and Wakefulness Research
- Genetics, Aging, and Longevity in Model Organisms
- Peptidase Inhibition and Analysis
- Amyotrophic Lateral Sclerosis Research
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Adenosine and Purinergic Signaling
- Autophagy in Disease and Therapy
- Neuroinflammation and Neurodegeneration Mechanisms
- Lysosomal Storage Disorders Research
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Neurological disorders and treatments
- Signaling Pathways in Disease
- Pluripotent Stem Cells Research
- Neurobiology and Insect Physiology Research
Johns Hopkins Medicine
2014-2022
Johns Hopkins University
2014-2022
Orthopaedic Research Foundation
2021
Drexel University
2012-2013
Philadelphia University
2013
Mutations in PINK1 and parkin cause autosomal recessive Parkinson's disease (PD). Evidence placing common pathways regulating multiple aspects of mitochondrial quality control is burgeoning. However, compelling evidence to causatively link specific PINK1/parkin dependent dopamine neuron degeneration PD lacking. Although are known regulate mitophagy, emerging data suggest that defects mitophagy unlikely be pathological relevance. Mitochondrial functions also tied their proteasomal regulation...
Histone acetylation of chromatin promotes dynamic transcriptional responses in neurons that influence neuroplasticity critical for cognitive ability. It has been demonstrated Tip60 histone acetyltransferase (HAT) activity is involved the regulation genes enriched neuronal function as well control synaptic plasticity. Accordingly, implicated neurodegenerative disorder Alzheimer's disease (AD) via regulatory complex formation with AD linked amyloid precursor protein (APP) intracellular domain...
Farnesol enhances the amounts of farnesylated PARIS and PGC-1α, preventing dopaminergic neuronal loss in Parkinson’s disease models.
Axonal transport defects and axonopathy are prominent in early preclinical stages of Alzheimer's disease (AD), often preceding known disease-related pathology by over a year. As epigenetic transcriptional regulatory mechanisms, such as histone acetylation, critical for neurogenesis, it is postulated that their misregulation might be linked to pathophysiological mechanisms contribute AD. The acetyltransferase (HAT) Tip60 epigenetically regulates genes enriched neuronal functions implicated AD...
Tip60 is a histone acetyltransferase (HAT) enzyme that epigenetically regulates genes enriched for neuronal functions through interaction with the amyloid precursor protein (APP) intracellular domain. However, whether Tip60-mediated epigenetic dysregulation affects specific processes in vivo and contributes to neurodegeneration remains unclear. Here, we show HAT activity mediates axonal growth of Drosophila pacemaker cells, termed "small ventrolateral neurons" (sLNvs), their production...
Dynamic epigenetic regulation of neurons is emerging as a fundamental mechanism by which adapt their transcriptional responses to specific developmental and environmental cues. While defects within the neural epigenome have traditionally been studied in context early heritable cognitive disorders, recent studies point aberrant histone acetylation status key underlying acquired inappropriate alterations genome structure function post-mitotic during aging process. Indeed, it becoming...
Mutations in PINK1 and parkin highlight the mitochondrial axis of Parkinson’s disease (PD) pathogenesis. PINK1/parkin regulation transcriptional repressor PARIS bears direct relevance to dopamine neuron survival through augmentation PGC-1α–dependent biogenesis. Notably, knockout attenuates dopaminergic neurodegeneration mouse models, indicating that interventions prevent accumulation could have therapeutic potential PD. To this end, we identified deubiquitinase cylindromatosis (CYLD) be a...
Sleep disturbances are common in neurodegenerative diseases such as Alzheimer disease (AD). Unfortunately, how AD is mechanistically linked with interference of the body's natural sleep rhythms remains unclear. Our recent findings provide insight into this question by demonstrating that disruption associated driven epigenetic changes mediated histone acetyltransferase (HAT) Tip60. In study, we show Tip60 functionally interacts amyloid precursor protein (APP) to regulate axonal growth...
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects over million people within the U.S. Underlying clinical symptoms of PD degeneration dopamine (DA) neurons located in pars compacta substantia nigra (SNpc). Microglial activation NLRP3 inflammasome has been well‐documented various diseases, including PD. We report herein adult onset conditional knockdown Parkin mouse SNpc results priming and neurons. These were replicated knockout generated human embryonic stem...
Modulating Epigenetic HAT Activity: A Promising Therapeutic Option for Neurological Disease? The epigenome (epi- derived from Greek ‘over’ or ‘above’) with its rich cache of highly regulated structural modifications to the DNA, histone residues and variants, defines threedimensional structure chromatin, genetic material within eukaryotic cell nucleus, serves as molecular bridge between transcriptional gene control our environment.