Fabry disease-associated globotriaosylceramide induces mechanical allodynia via activation of signaling through proNGF-p75
Autor: | Junya, Sugimoto, Hiroshi, Satoyoshi, Kazue, Takahata, Shizuko, Muraoka |
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Rok vydání: | 2020 |
Předmět: |
Male
Pain Threshold Analgesics Trihexosylceramides Receptors Nerve Growth Factor Antibodies Neutralizing Cyclic AMP-Dependent Protein Kinases Mice Inbred C57BL Disease Models Animal Membrane Microdomains Hyperalgesia Ganglia Spinal Nerve Growth Factor Animals Protein Precursors Receptor trkA Signal Transduction Skin |
Zdroj: | European journal of pharmacology. 895 |
ISSN: | 1879-0712 |
Popis: | Fabry disease (FD) is an X-linked metabolic storage disorder arising from the deficiency of lysosomal α-galactosidase A, which leads to the gradual accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3), throughout the body. Pain in the extremities is an early symptom of FD; however, the underlying pathophysiological mechanisms remain unknown. α-Galactosidase A knockout animals exhibit nociceptive behaviors, with enhanced expression levels of several ion channels. These characteristics are observed in animals treated with nerve growth factor (NGF). Here, we aimed to elucidate the potential of NGF signaling as a cause of FD-associated pain, using intraplantar Gb3-treated mice displaying mechanical allodynia. Treatment with a neutralizing antibody against a precursor of NGF (proNGF) or its receptor, p75 neurotrophin receptor (p75 |
Databáze: | OpenAIRE |
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