The Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia.
Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, WA 6150, Australia.
Int J Mol Sci. 2022 Aug 19;23(16):9364. doi: 10.3390/ijms23169364.
Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease classified as both a neurodegenerative and neuromuscular disorder. With a complex aetiology and no current cure for ALS, broadening the understanding of disease pathology and therapeutic avenues is required to progress with patient care. Alpha-synuclein (αSyn) is a hallmark for disease in neurodegenerative disorders, such as Parkinson's disease, Lewy body dementia, and multiple system atrophy. A growing body of evidence now suggests that αSyn may also play a pathological role in ALS, with αSyn-positive Lewy bodies co-aggregating alongside known ALS pathogenic proteins, such as and TDP-43. This review endeavours to capture the scope of literature regarding the aetiology and development of ALS and its commonalities with "synucleinopathy disorders". We will discuss the involvement of αSyn in ALS and motor neuron disease pathology, and the current theories and strategies for therapeutics in ALS treatment, as well as those targeting αSyn for synucleinopathies, with a core focus on small molecule RNA technologies.
肌萎缩侧索硬化症（ALS）是最常见的成年起病的运动神经元疾病，既属于神经退行性疾病，也属于神经肌肉疾病。由于 ALS 的病因复杂，目前尚无治愈方法，因此需要加深对疾病病理和治疗途径的理解，以改善患者的治疗效果。α-突触核蛋白（αSyn）是神经退行性疾病（如帕金森病、路易体痴呆和多系统萎缩）的标志性疾病蛋白。越来越多的证据表明，αSyn 可能在 ALS 中也发挥病理性作用，αSyn 阳性路易体与已知的 ALS 致病蛋白（如 FUS 和 TDP-43）共同聚集。本综述旨在阐述 ALS 的病因和发病机制及其与“突触核蛋白病”的共同之处。我们将讨论 αSyn 在 ALS 和运动神经元疾病病理中的作用，以及目前针对 ALS 治疗的治疗策略和针对突触核蛋白病的治疗策略，重点关注小分子 RNA 技术。
