Murphy Kate T, Lynch Gordon S
Department of Anatomy and Physiology, Centre for Muscle Research, The University of Melbourne, Melbourne, Australia.
J Cachexia Sarcopenia Muscle. 2023 Oct;14(5):1987-2002. doi: 10.1002/jcsm.13312. Epub 2023 Aug 13.
There is increasing evidence that neurodegenerative disorders including the Parkinsonian syndromes are associated with impaired skeletal muscle health, manifesting as wasting and weakness. Many of the movement problems, lack of muscle strength and reduction in quality of life that are characteristic of these syndromes can be attributed to impairments in skeletal muscle health, but this concept has been grossly understudied and represents an important area of unmet clinical need. This review describes the changes in skeletal muscle health in idiopathic Parkinson's disease and in two atypical Parkinsonian syndromes, the most aggressive synucleinopathy multiple system atrophy, and the tauopathy progressive supranuclear palsy. The pathogenesis of the skeletal muscle changes is described, including the contribution of impairments to the central and peripheral nervous system and intrinsic alterations. Pharmacological interventions targeting the underlying molecular mechanisms with therapeutic potential to improve skeletal muscle health in affected patients are also discussed. Although little is known about the mechanisms underlying these conditions, current evidence implicates multiple pathways and processes, highlighting the likely need for combination therapies to protect muscle health and emphasizing the merit of personalized interventions for patients with different physical capacities at different stages of their disease. As muscle fatigue is often experienced by patients prior to diagnosis, the identification and measurement of this symptom and related biomarkers to identify early signs of disease require careful interrogation, especially for multiple system atrophy and progressive supranuclear palsy where diagnosis is often made several years after onset of symptoms and only confirmed post-mortem. We propose a multidisciplinary approach for early diagnosis and implementation of personalized interventions to preserve muscle health and improve quality of life for patients with typical and atypical Parkinsonian syndromes.
越来越多的证据表明，包括帕金森综合征在内的神经退行性疾病与骨骼肌健康受损有关，表现为肌肉萎缩和无力。这些综合征所特有的许多运动问题、肌肉力量不足和生活质量下降都可归因于骨骼肌健康受损，但这一概念一直未得到充分研究，是临床需求未得到满足的一个重要领域。本综述描述了特发性帕金森病以及两种非典型帕金森综合征（最具侵袭性的突触核蛋白病多系统萎缩和tau蛋白病进行性核上性麻痹）中骨骼肌健康的变化。文中描述了骨骼肌变化的发病机制，包括中枢和外周神经系统损伤以及内在改变的作用。还讨论了针对潜在分子机制的药物干预措施，这些措施具有改善受影响患者骨骼肌健康的治疗潜力。尽管对这些病症的潜在机制了解甚少，但目前的证据涉及多种途径和过程，这凸显了可能需要联合治疗来保护肌肉健康，并强调了针对疾病不同阶段具有不同身体能力的患者进行个性化干预的价值。由于患者在诊断前经常会经历肌肉疲劳，因此对这种症状和相关生物标志物的识别和测量以确定疾病的早期迹象需要仔细研究，特别是对于多系统萎缩和进行性核上性麻痹，其诊断往往在症状出现数年之后，且只有在尸检后才能得到证实。我们提出了一种多学科方法，用于早期诊断和实施个性化干预措施，以保护肌肉健康并提高典型和非典型帕金森综合征患者的生活质量。
