Nuclear localization of SMN and FUS is not altered in fibroblasts from patients with sporadic ALS

Abstract

Sporadic amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no established biological marker. Recent observation of a reduced number of gems (survival motor neuron protein (SMN)-positive nuclear bodies) in cells from patients with familial ALS and the mouse models suggests an involvement of SMN in ALS pathology. At a molecular level, fused in sarcoma (FUS), one of the familial ALS-linked proteins, has been demonstrated to directly interact with SMN, while impaired nuclear localization of mutated FUS causes defective gem formation. Our objective was to determine whether gems and/or nuclear FUS levels in skin derived fibroblasts from sporadic ALS patients are consistently reduced and thus could constitute a novel and readily available biomarker of the disease. Fibroblasts from 20 patients and 17 age-matched healthy controls were cultured and co-immunostained for SMN and FUS. Results showed that no difference was detected between the two groups in the number of gems and in expression pattern of FUS. The number of gems negatively correlated with the age at biopsy in both ALS and control subjects. In conclusion, the expression pattern of SMN and FUS in fibroblasts cannot serve as a biomarker for sporadic ALS. Donor age-dependent gem reduction is a novel observation that links SMN with cellular senescence.

Key words::

• Gem
• SMN
• FUS
• sporadic ALS
• fibroblast
• donor age

Acknowledgements

We acknowledge the patients with ALS and healthy subjects who participated in the study. The authors thank Jonathan Hupf, Nicole Armstrong, Yei-Won Lee, and Jess Singleton for their assistance in summarizing patient clinical history, and Saba Tadesse for organizing fibroblast samples. We are grateful to doctors Przedborski and Monani for their valuable suggestions. Skin biopsies were obtained as part of the multicenter study of ALS COSMOS project (R01ES160348) to HM. Healthy control skin biopsies were obtained under MDA Wings Over Wall Street grant (HM). DBR is a recipient of a Career Development Award from the NIEHS Center of Northern Manhattan (ES009089).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.