A5075121265- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Alzheimer's disease research and treatments
- Dermatology and Skin Diseases
- Fish Ecology and Management Studies
- Fish Biology and Ecology Studies
- Neuroscience and Neuropharmacology Research
- Ubiquitin and proteasome pathways
- Hypothalamic control of reproductive hormones
- Urticaria and Related Conditions
- Neurotransmitter Receptor Influence on Behavior
- Cancer, Stress, Anesthesia, and Immune Response
- Asthma and respiratory diseases
- 14-3-3 protein interactions
- Glycosylation and Glycoproteins Research
- Stress Responses and Cortisol
- Tryptophan and brain disorders
- Aquatic Ecosystems and Biodiversity
- Neuroinflammation and Neurodegeneration Mechanisms
- Chemokine receptors and signaling
- Eicosanoids and Hypertension Pharmacology
- interferon and immune responses
- Pharmacological Receptor Mechanisms and Effects
- Cholinesterase and Neurodegenerative Diseases
Wake Forest University
2015-2023
Wakayama Medical University
2015-2021
W. G. (Bill) Hefner VA Medical Center
2021
Predictive Biology (United States)
2021
University of Padua
2021
University of Ferrara
2021
Xiangya Hospital Central South University
2021
Central South University
2021
Huazhong Agricultural University
2017-2019
Chinese Academy of Sciences
2000-2019
Histone deacetylase 6 (HDAC6), a unique cytoplasmic deacetylase, likely plays role in neurodegeneration by coordinating cell responses to abnormal protein aggregation. Here, we provide vitro and vivo evidence that HDAC6 interacts with tau, microtubule-associated forms neurofibrillary tangles Alzheimer's disease. This interaction is mediated the microtubule-binding domain on tau Ser/Glu tetradecapeptide HDAC6. Treatment tubacin, selective inhibitor of tubulin deacetylation activity HDAC6, did...
The small-molecule AT-121 is an agonist of nociceptin and mu opioid peptide receptors mediates analgesia without opioid-associated side effects in nonhuman primates.
Significance A potent opioid analgesic without addictive and respiratory adverse effects has been a predominant goal for medicinal chemistry since the isolation of morphine from opium in 19th century. Here we report functional profile unique analog, BU08028, targeting combination classical nonclassical receptors monkeys. By examining behavioral, physiological, pharmacologic factors, present study demonstrates that BU08028 exhibits full antinociception antihypersensitivity reinforcing (i.e.,...
Chronic allergic itch is a common symptom affecting millions of people and animals, but its pathogenesis not fully explained. Herein, we show that periostin, abundantly expressed in the skin patients with atopic dermatitis (AD), induces mice, dogs, monkeys. We identify integrin αVβ3 on subset sensory neurons as periostin receptor. Using pharmacological genetic approaches, inhibited function neuronal αVβ3, which significantly reduces periostin-induced mice. Furthermore, cytokine TSLP,...
Background & AimsLimited understanding of pruritus mechanisms in cholestatic liver diseases hinders development antipruritic treatments. Previous studies implicated lysophosphatidic acid (LPA) as a potential mediator pruritus.MethodsPruritogenicity lysophosphatidylcholine (LPC), LPA's precursor, was examined naïve mice, and nonhuman primates. LPC's pruritogenicity involving keratinocyte TRPV4 studied using genetic pharmacologic approaches, cultured keratinocytes, ion channel physiology,...
PD-1 regulates opioid signaling in primary sensory and spinal cord neurons plays a critical role antinociception.
The microtubule-associated protein tau is hyperphosphorylated and forms neurofibrillary tangles in Alzheimer disease. Additionally caspase-cleaved present disease brains co-localized with fibrillar pathologies. To further understand the role of site-specific phosphorylation caspase cleavage regulating its function, constructs full-length (T4) or truncated at Asp<sup>421</sup> (T4C3) to mimic caspase-3 without site-directed mutations that Thr<sup>231</sup>/Ser<sup>235</sup>,...
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common known cause of inherited Parkinson's disease (PD), and LRRK2 is a risk factor for idiopathic PD. How function regulated not well understood. Recently, highly conserved 14-3-3 proteins, which play key role many cellular functions including cell death, have been shown to interact with LRRK2. In this study, we investigated whether 14-3-3s can regulate mutant LRRK2-induced neurite shortening activity. presence 14-3-3θ...
Pur-alpha (Purα) plays an important role in a variety of cellular processes including transcriptional regulation, cell proliferation and oncogenic transformation. To better understand the Purα developing mature brain, we generated Purα-deficient mice, which were able to raise age six months. Purα(-/-) mice born with no obvious pathological condition. We obtained convincing evidence that lack prolongs postnatal neuronal precursor cells both hippocampus cerebellum, however, without affecting...
Morphine-induced itch is mediated by a specific population of dynorphin-expressing spinal inhibitory neurons in mice.
Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor agonists display a promising analgesic profile in preclinical studies. However, supraspinal N/OFQ produced hyperalgesia rodents and such effects have not been addressed primates. Thus, the aim of this study was to investigate centrally administered ligands on regulating pain itch non-human In particular, nociceptive thresholds affected by intracisternal were compared with those morphine substance P, known provide analgesia mediate...
The angiogenic factor, angiogenin, has been recently linked to both Amyotrophic Lateral Sclerosis (ALS) and Parkinson Disease (PD). We have shown that endogenous angiogenin levels are dramatically reduced in an alpha-synuclein mouse model of PD exogenous protects against cell loss neurotoxin-based cellular models PD. Here, we extend our studies examine whether activation the prosurvival Akt pathway is required for angiogenin's neuroprotective effects 1-methyl-4-phenylpyridinium (MPP+), as...
B-type natriuretic peptide (BNP)–natriuretic receptor A (NPRA) and gastrin-releasing (GRP)–GRP (GRPR) systems contribute to spinal processing of itch. However, pharmacological anatomic evidence these two ligand-receptor are still not clear. The aim this study was determine the functions BNP-NPRA GRP-GRPR for regulating scratching activities in mice by using immunohistochemical approaches. Our results showed that intrathecal administration BNP (0.3–3 nmol) dose dependently elicited responses,...
Background and purpose Using an innovative chemical approach, peptide welding technology ( PWT ), a tetrabranched derivative of nociceptin/orphanin FQ N / OFQ ) has been generated pharmacologically characterized. Both in vitro vivo 2‐ displayed the same pharmacological profile to natural ligand. It was more potent produced longer‐lasting effects. The aim present study investigate spinal effects nociceptive neuropathic pain models mice non‐human primates. Experimental Approach Tail withdrawal...