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[Lysophosphatidic Acid Receptor Signaling Underlying Chronic Pain and Neuroprotective Mechanisms through Prothymosin α].
Ueda, Hiroshi.
Afiliação
  • Ueda H; Department of Pharmacology and Therapeutic Innovation, Nagasaki University, Institute of Biomedical Sciences.
Yakugaku Zasshi ; 139(11): 1403-1415, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31685737
ABSTRACT
For my Ph.D. research topic, I isolated endogenous morphine-like analgesic dipeptide, kyotorphin, which mediates Met-enkephalin release, and discovered kyotorphin synthetase, a putative receptor and antagonist. Furthermore, I succeeded in purifying µ-opioid receptor and functional reconstitution with purified G proteins. After receiving my full professor position at Nagasaki University in 1996, I worked on two topics of research, molecular mechanisms of chronic pain through lysophosphatidic acid (LPA) and identification and characterization of neuroprotective protein, prothymosin α. In a series of studies, we have shown that LPA signaling defines the molecular mechanisms of neuropathic pain and fibromyalgia in terms of development and maintenance. Above all, the discovery of feed-forward system in LPA production and pain memory may contribute to better understanding of chronic pain and future analgesic drug discovery. Regarding prothymosin α, we first discovered it as neuronal necrosis-inhibitory molecule through two independent mechanisms, such as toll-like receptor and F0/F1 ATPase, both which protect neurons through indirect mechanisms. Prothymosin α is released by non-classical and non-vesicular mechanisms on various stresses, such as ischemia, starvation, and heat-shock. Thus it may be called a new type of neuroprotective damage-associated molecular patterns (DAMPs)/Alarmins. Heterozygotic mice showed a defect in memory-learning and neurogenesis as well as anxiogenic behaviors. Small peptide, P6Q derived from prothymosin α retains neuroprotective actions, which include blockade of cerebral hemorrhage caused by late treatment with tissue plasminogen activator in the stroke model in mice.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Precursores de Proteínas / Timosina / Transdução de Sinais / Fármacos Neuroprotetores / Receptores de Ácidos Lisofosfatídicos / Dor Crônica Limite: Animais / Humanos Idioma: Japonês Revista: Yakugaku Zasshi Ano de publicação: 2019 Tipo de documento: Artigo