정회윤 (노브메타파마, POSTECH) | 한빛사논문 > 한빛사

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조회536

노브메타파마, POSTECH

Adv. Sci., May 10 2024, | https://doi.org/10.1002/advs.202305927 Cyclo His-Pro Attenuates Muscle Degeneration in Murine Myopathy Models

Alessia De Masi ¹, Nadège Zanou ², Keno Strotjohann¹, Dohyun Lee ³, Tanes I. Lima ¹, Xiaoxu Li ¹, Jongsu Jeon ³, Nicolas Place ², Hoe-Yune Jung ^3,4, Johan Auwerx ¹

¹Laboratory of Integrative Systems Physiology, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland.

²Institute of Sport Sciences and Department of Biomedical Sciences, Faculty of Biology-Medicine, University of Lausanne, Lausanne, 1015, Switzerland.

³R&D Center, NovMetaPharma Co., Ltd, Pohang, 37668, South Korea.

⁴School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673, South Korea.

N.Z., K.S., and D.L. contributed equally as co-second authors.

CORRESPONDING AUTHORS: Hoe-Yune Jung, Johan Auwerx

Abstract

Among the inherited myopathies, a group of muscular disorders characterized by structural and metabolic impairments in skeletal muscle, Duchenne muscular dystrophy (DMD) stands out for its devastating progression. DMD pathogenesis is driven by the progressive degeneration of muscle fibers, resulting in inflammation and fibrosis that ultimately affect the overall muscle biomechanics. At the opposite end of the spectrum of muscle diseases, age-related sarcopenia is a common condition that affects an increasing proportion of the elderly. Although characterized by different pathological mechanisms, DMD and sarcopenia share the development of progressive muscle weakness and tissue inflammation. Here, the therapeutic effects of Cyclo Histidine-Proline (CHP) against DMD and sarcopenia are evaluated. In the mdx mouse model of DMD, it is shown that CHP restored muscle contractility and force production, accompanied by the reduction of fibrosis and inflammation in skeletal muscle. CHP furthermore prevented the development of cardiomyopathy and fibrosis in the diaphragm, the two leading causes of death for DMD patients. CHP also attenuated muscle atrophy and functional deterioration in a mouse model of age-related sarcopenia. These findings from two different models of muscle dysfunction hence warrant further investigation into the effects of CHP on muscle pathologies in animal models and eventually in patients.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-13)
연구진국내(교신)+국외 연구진
분야 생명과학 > 생리학

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