Brain and Mind Centre, Faculty of Medicine and Health, School of Medical Sciences, University of Sydney, Camperdown, New South Wales, Australia
Department of Neurology, Neuromuscular Division, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
J Neurol Neurosurg Psychiatry. 2023 Nov;94(11):962-972. doi: 10.1136/jnnp-2021-328323. Epub 2023 Apr 4.
Multiple pathological mechanisms are involved in the development of chemotherapy-induced peripheral neurotoxicity (CIPN). Recent work has provided insights into the molecular mechanisms underlying chemotherapy-induced axonal degeneration. This review integrates evidence from preclinical and clinical work on the onset, progression and outcome of axonal degeneration in CIPN. We review likely triggers of axonal degeneration in CIPN and highlight evidence of molecular pathways involved in axonal degeneration and their relevance to CIPN, including SARM1-mediated axon degeneration pathway. We identify potential clinical markers of axonal dysfunction to provide early identification of toxicity as well as present potential treatment strategies to intervene in axonal degeneration pathways. A greater understanding of axonal degeneration processes in CIPN will provide important information regarding the development and progression of axonal dysfunction more broadly and will hopefully assist in the development of successful interventions for CIPN and other neurodegenerative disorders.
多种病理机制参与了化疗引起的周围神经毒性（CIPN）的发展。最近的研究为化疗诱导的轴突变性的分子机制提供了深入的了解。本综述综合了临床前和临床研究中关于 CIPN 中轴突变性的起始、进展和结果的证据。我们综述了 CIPN 中轴突变性的可能触发因素，并强调了涉及轴突变性的分子途径及其与 CIPN 的相关性，包括 SARM1 介导的轴突变性途径。我们确定了潜在的轴突功能障碍的临床标志物，以提供对毒性的早期识别，并提出了潜在的治疗策略来干预轴突变性途径。对 CIPN 中轴突变性过程的更深入了解将为更广泛的轴突功能障碍的发展和进展提供重要信息，并有望有助于成功干预 CIPN 和其他神经退行性疾病。
