A5038058198- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Neuroscience and Neuropharmacology Research
- Ubiquitin and proteasome pathways
- Alzheimer's disease research and treatments
- Epigenetics and DNA Methylation
- Cholinesterase and Neurodegenerative Diseases
- Multiple Myeloma Research and Treatments
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- Computational Drug Discovery Methods
- Sleep and Wakefulness Research
- Tryptophan and brain disorders
- Neurogenesis and neuroplasticity mechanisms
- Pharmacological Receptor Mechanisms and Effects
- Neuroinflammation and Neurodegeneration Mechanisms
- Pain Mechanisms and Treatments
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
- Peptidase Inhibition and Analysis
- Inflammasome and immune disorders
- Central Asia Education and Culture
- Cannabis and Cannabinoid Research
- interferon and immune responses
- Retinoids in leukemia and cellular processes
Athinoula A. Martinos Center for Biomedical Imaging
2016-2025
Harvard University
2015-2025
Massachusetts General Hospital
2015-2025
Harvard University Press
2014-2023
Gannan Normal University
2023
China National Petroleum Corporation (China)
2012-2021
State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation
2021
Center for Pain and the Brain
2020
Stomatology Hospital
2019
Wuhan University
2019
Epigenetic enzymes are now targeted to treat the underlying gene expression dysregulation that contribute disease pathogenesis. Histone deacetylases (HDACs) have shown broad potential in treatments against cancer and emerging data supports their targeting context of cardiovascular central nervous system dysfunction. Development a molecular agent for non-invasive imaging elucidate distribution functional roles HDACs humans will accelerate medical research drug discovery this domain. Herein,...
BACKGROUND: Gut microbiota, a consortium of diverse microorganisms residing in the gastrointestinal tract, has emerged as key player neuroinflammatory responses, supporting functional relevance “gut–brain axis.” Chronic-constriction injury sciatic nerve (CCI) is commonly used animal model neuropathic pain with major input from T cell–mediated immune responses. In this article, we sought to examine whether gut microbiota influences CCI pain, and, if so, T-cell responses are implicated....
Myelination represents one of the most fundamental biological processes in vertebrate nervous system. Abnormalities and changes myelination central system (CNS) are seen many neurodegenerative disorders, such as multiple sclerosis (MS). A long-standing goal has been to directly detect quantify myelin content order facilitate diagnosis therapeutic treatments myelin-related diseases. In course our studies, we have developed a series small-molecule probes (SMP) myelin-imaging agents. Among them...
Patients with schizophrenia (SCZ) experience chronic cognitive deficits. Histone deacetylases (HDACs) are enzymes that regulate circuitry; however, the role of HDACs in disorders, including SCZ, remains unknown humans. We previously determined HDAC2 mRNA levels were lower dorsolateral prefrontal cortex (DLPFC) tissue from donors SCZ compared controls. Here we investigated relationship between vivo HDAC expression and impairment patients matched healthy controls using [11C]Martinostat...
Abstract INTRODUCTION Blood phosphorylated tau at threonine 217 (tau‐PT217) is a newly established biomarker for Alzheimer's disease and postoperative delirium in patients. However, the mechanisms consequences of acute changes blood tau‐PT217 remain largely unknown. METHODS We investigated effects anesthesia/surgery on aged mice, evaluated associated B cell populations, neuronal excitability anterior cingulate cortex, delirium‐like behavior using positron emission tomography imaging,...
Recent studies have shown that the epigenetic protein histone deacetylase 11 (HDAC11) is highly expressed in brain and critically modulates neuroimmune functions, making it a potential therapeutic target for neurological disorders. Herein, we report development of PB94, which novel HDAC11 inhibitor. PB94 exhibited potency selectivity against with IC50 = 108 nM >40-fold over other HDAC isoforms. Pharmacokinetic/pharmacodynamic evaluation indicated possesses promising drug-like properties....
Purpose: Orexin receptors (OXRs) play a crucial role in modulating various physiological and neuropsychiatric functions within the central nervous system (CNS). Despite their significance, precise of OXRs brain remains elusive. Positron emission tomography (PET) imaging is instrumental unraveling CNS functions, development specific PET tracers for current research focus. Methods: The study investigated MDK-5220, an OX2R-selective agonist with promising binding properties (EC 50 on OX 2 R:...
The serotonin subtype 2C (5HT2C) receptor is an emerging and promising drug target to treat several disorders of the human central nervous system. In this current report, two potent selective 5HT2C full agonists, WAY-163909 (2) vabicaserin (3), were radiolabeled with carbon-11 via Pictet-Spengler cyclization [(11)C]formaldehyde used in positron emission tomography (PET) imaging. Reaction conditions optimized exclude major source isotope dilution caused by previously unknown breakdown...
Abstract Age- and sex-related alterations in gene transcription have been demonstrated, however the underlying mechanisms are unresolved. Neuroepigenetic pathways regulate brain. Here, we measure vivo expression of epigenetic enzymes, histone deacetylases (HDACs), across healthy human aging between sexes using [ 11 C]Martinostat positron emission tomography (PET) neuroimaging ( n = 41). Relative HDAC increases with age cerebral white matter, correlates age-associated disruptions matter...
Although the epigenetic regulatory protein histone deacetylase 6 (HDAC6) has been recently implicated in etiology of Alzheimer's disease (AD), little is known about role HDAC6 etiopathogenesis AD and whether can be a potential therapeutic target for AD. Here, we performed positron emission tomography (PET) imaging combination with histopathological analysis to better understand underlying pathomechanisms We first developed [18F]PB118 which was demonstrated as valid radioligand excellent...
Abstract Alzheimer’s disease (AD) is characterized by the brain accumulation of amyloid-β and tau proteins. A growing body literature suggests that epigenetic dysregulations play a role in interplay hallmark proteinopathies with neurodegeneration cognitive impairment. Here, we aim to characterize an dysregulation associated deposition Using positron emission tomography (PET) tracers selective for amyloid-β, tau, class I histone deacetylase (HDAC isoforms 1–3), find HDAC levels are reduced...
Optical three-dimensional (3D) molecular imaging is highly desirable for providing precise distribution of the target-of-interest in disease models. However, such 3D still far from wide applications biomedical research; brain optical imaging, particular, has rarely been reported. In this report, we designed chemiluminescence probes with high quantum yields, relatively long emission wavelengths, and signal-to-noise ratios to fulfill requirements vivo. With assistance density-function theory...
Abstract Chronic pain is highly prevalent and linked to a broad range of comorbidities, including sleep disorders. Epidemiological clinical evidence suggests that chronic disruption (CSD) leads heightened sensitivity, referred as CSD-induced hyperalgesia. However, the underlying mechanisms are unclear. The thalamic reticular nucleus (TRN) has unique integrative functions in sensory processing, attention/arousal spindle generation. We report TRN played an important role hyperalgesia mice,...
Abstract INTRODUCTION Alzheimer's disease (AD) is characterized by amyloid pathology and neuroinflammation, leading to cognitive decline. Targeting histone deacetylase‐11 (HDAC11) offers a novel therapeutic strategy due its role in immune regulation. METHODS We conducted neuropathological analyses on human AD post mortem brain tissues 5xFAD transgenic mice. developed PB94, brain‐permeable HDAC11‐selective inhibitor, assessed effects using live‐animal imaging behavioral studies. RESULTS...
BET proteins are essential epigenetic regulators involved in gene transcription and have been linked to neurodegenerative disorders, such as Alzheimer's disease (AD). In vivo imaging of may provide insights into pathophysiology help identify potential therapeutic targets. We developed a carbon-11-labeled radiotracer, [11C]YL9, which exhibits high binding affinity for proteins. It was synthesized via standard methylation evaluated brain uptake, specificity, pharmacokinetics wild-type AD mouse...
Background: Post-operative delirium (POD) is a common and serious clinical condition that occurs following anesthesia/surgery. While its impact well recognized, the underlying electrophysiological mechanisms remain largely unknown, posing challenges for effective treatment. This study aims to investigate hippocampal neural dynamics before after anesthesia/surgery in aged mice, which have tendency of developing POD. Methods: included adult mice with POD model. POD-like behavior was assessed N...
Destruction or changes associated with myelin membranes in the CNS play a key role pathogenesis of multiple sclerosis and other related neurodegenerative disorders. A long-standing goal has been to detect quantify content vivo . For this reason, we have developed myelin-imaging technique based on positron emission tomography (PET). PET is quantitative imaging modality that widely used clinical settings for direct assessment biological processes at molecular level. However, lack probes...
Myelination is one of the fundamental biological processes in development vertebrate nervous system. Disturbance myelination found to be associated with progression many neurological diseases such as multiple sclerosis. Tremendous efforts have been made develop novel therapeutic agents that prevent demyelination and/or promote remyelination. These need accompanied by imaging tools permit direct quantification vivo . In this work, we describe a near-infrared fluorescence technique capable...
We describe a novel fluorescent dye, 3-(4-aminophenyl)-2 H-chromen-2-one (termed case myelin compound or CMC), that can be used for in situ imaging of the vertebrate nervous system. When administered via intravenous injection into tail vein, CMC selectively stained large bundles myelinated fibers both central system (CNS) and peripheral (PNS). In CNS, readily entered brain localized regions such as corpus callosum cerebellum. also nerves PNS. The staining patterns hypermyelinated mouse model...
Epigenetic mechanisms mediated by histone deacetylases (HDACs) have been implicated in a wide-range of CNS disorders and may offer new therapeutic opportunities. In vivo evaluation HDAC density drug occupancy has become possible with [11C]Martinostat, which exhibits selectivity for subset class I/IIb enzymes. this study, we characterize the kinetic properties [11C]Martinostat nonhuman primate (NHP) brain preparation human neuroimaging studies. The goal work was to determine whether classic...
Epigenetic regulation plays substantial roles in human pathophysiology, which provides opportunities for intervention disorders through the targeting of epigenetic pathways. Recently, emerging evidence from preclinical studies suggested potential developing therapeutics Alzheimer's disease (AD) by bromodomain containing protein 4 (BRD4), an regulatory protein. However, further characterization AD-related pathological events is urgently required. Here, we investigated effects pharmacological...