Morani Federica, Doccini Stefano, Galatolo Daniele, Pezzini Francesco, Soliymani Rabah, Simonati Alessandro, Lalowski Maciej M, Gemignani Federica, Santorelli Filippo M
Department of Biology, University of Pisa, 56126 Pisa, Italy.
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit-IRCCS Stella Maris, 56128 Pisa, Italy.
Biomolecules. 2022 Jul 24;12(8):1024. doi: 10.3390/biom12081024.
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an inherited neurodegenerative disease characterized by early-onset spasticity in the lower limbs, axonal-demyelinating sensorimotor peripheral neuropathy, and cerebellar ataxia. Our understanding of ARSACS (genetic basis, protein function, and disease mechanisms) remains partial. The integrative use of organelle-based quantitative proteomics and whole-genome analysis proposed in the present study allowed identifying the affected disease-specific pathways, upstream regulators, and biological functions related to ARSACS, which exemplify a rationale for the development of improved early diagnostic strategies and alternative treatment options in this rare condition that currently lacks a cure. Our integrated results strengthen the evidence for disease-specific defects related to bioenergetics and protein quality control systems and reinforce the role of dysregulated cytoskeletal organization in the pathogenesis of ARSACS.
夏尔沃 - 萨格奈常染色体隐性痉挛性共济失调（ARSACS）是一种遗传性神经退行性疾病，其特征为下肢早发性痉挛、轴索性脱髓鞘感觉运动性周围神经病和小脑共济失调。我们对ARSACS（遗传基础、蛋白质功能和疾病机制）的了解仍然有限。本研究中提出的基于细胞器的定量蛋白质组学和全基因组分析的综合应用，有助于识别与ARSACS相关的受影响疾病特异性途径、上游调节因子和生物学功能，这为在目前尚无治愈方法的这种罕见疾病中开发改进的早期诊断策略和替代治疗方案提供了理论依据。我们的综合结果强化了与生物能量学和蛋白质质量控制系统相关的疾病特异性缺陷的证据，并加强了细胞骨架组织失调在ARSACS发病机制中的作用。
