Angelopoulou Efthalia, Paudel Yam Nath, Villa Chiara, Piperi Christina
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor 47500, Malaysia.
Brain Sci. 2020 Oct 7;10(10):713. doi: 10.3390/brainsci10100713.
Parkinson's disease (PD), the second most common neurodegenerative disorder after Alzheimer's disease, is a clinically heterogeneous disorder, with obscure etiology and no disease-modifying therapy to date. Currently, there is no available biomarker for PD endophenotypes or disease progression. Accumulating evidence suggests that mutations in genes related to lysosomal function or lysosomal storage disorders may affect the risk of PD development, such as gene mutations. In this context, recent studies have revealed the emerging role of arylsulfatase A (ASA), a lysosomal hydrolase encoded by the gene causing metachromatic leukodystrophy (MLD) in PD pathogenesis. In particular, altered ASA levels have been detected during disease progression, and reduced enzymatic activity of ASA has been associated with an atypical PD clinical phenotype, including early cognitive impairment and essential-like tremor. Clinical evidence further reveals that specific gene variants may act as genetic modifiers in PD. Recent in vitro and in vivo studies indicate that ASA may function as a molecular chaperone interacting with α-synuclein (SNCA) in the cytoplasm, preventing its aggregation, secretion and cell-to-cell propagation. In this review, we summarize the results of recent preclinical and clinical studies on the role of ASA in PD, aiming to shed more light on the potential implication of ASA in PD pathogenesis and highlight its biomarker potential.
帕金森病（PD）是仅次于阿尔茨海默病的第二常见神经退行性疾病，是一种临床异质性疾病，病因不明，迄今为止尚无疾病修饰疗法。目前，尚无用于PD内表型或疾病进展的生物标志物。越来越多的证据表明，与溶酶体功能或溶酶体贮积症相关的基因突变可能影响PD发生风险，如基因突变。在此背景下，最近的研究揭示了芳基硫酸酯酶A（ASA）在PD发病机制中的新作用，ASA是一种由导致异染性脑白质营养不良（MLD）的基因突变编码的溶酶体水解酶。特别是，在疾病进展过程中检测到ASA水平发生改变，且ASA酶活性降低与非典型PD临床表型相关，包括早期认知障碍和类特发性震颤。临床证据进一步表明，特定的基因突变可能在PD中充当遗传修饰因子。最近的体外和体内研究表明，ASA可能作为分子伴侣在细胞质中与α-突触核蛋白（SNCA）相互作用，防止其聚集、分泌和细胞间传播。在本综述中，我们总结了近期关于ASA在PD中作用的临床前和临床研究结果，旨在更深入了解ASA在PD发病机制中的潜在意义，并突出其作为生物标志物的潜力。
