Abstract:
OBJECTIVE:To investigate whether arginine methylation is altered in patients with amyotrophic lateral sclerosis (ALS) and how it affects disease severity, progression, and prognosis. METHODS:We compared the immunoreactivity of protein arginine methyltransferase 1 (PRMT1) and its products, asymmetric dimethylated proteins (ASYM), in postmortem spinal cord. We also measured the concentrations of total l-arginine and methylated arginine residues, including asymmetric dimethyl l-arginine (ADMA), symmetric dimethyl arginine, and monomethyl arginine, in CSF samples from 52 patients with ALS using liquid chromatography-tandem mass spectrometry, and we examined their relationship with the progression and prognosis of ALS. RESULTS:The immunoreactivity of both PRMT1 (p < 0.0001) and ASYM (p = 0.005) was increased in patients with ALS. The concentration of ADMA in CSF was substantially higher in patients with ALS than in disease controls. The ADMA/l-arginine ratio was correlated with the change of decline in the ALS Functional Rating Scale at 12 months after the time of measurement (r = 0.406, p = 0.010). A Cox proportional hazards model showed that the ADMA/l-arginine ratio was an independent predictor for overall survival. Moreover, a high ADMA/l-arginine ratio predicted poor prognosis, even in a group with normal percentage forced vital capacity. CONCLUSION:There was an enhancement of arginine dimethylation in patients with ALS, and the ADMA/l-arginine ratio predicted disease progression and prognosis in such patients.
journal_name
Neurologyjournal_title
Neurologyauthors
Ikenaka K,Atsuta N,Maeda Y,Hotta Y,Nakamura R,Kawai K,Yokoi D,Hirakawa A,Taniguchi A,Morita M,Mizoguchi K,Mochizuki H,Kimura K,Katsuno M,Sobue Gdoi
10.1212/WNL.0000000000007311subject
Has Abstractpub_date
2019-04-16 00:00:00pages
e1868-e1877issue
16eissn
0028-3878issn
1526-632Xpii
WNL.0000000000007311journal_volume
92pub_type
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