Increase of arginine dimethylation correlates with the progression and prognosis of ALS
Citation Manager Formats
Make Comment
See Comments

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
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.
Glossary
- ADMA=
- asymmetric dimethyl l-arginine;
- ALS=
- amyotrophic lateral sclerosis;
- ALSFRS-R=
- ALS Functional Rating Scale;
- ASYM=
- asymmetric dimethylated proteins;
- CI=
- confidence interval;
- CK=
- creatinine kinase;
- HR=
- hazard ratio;
- MMT=
- Manual Muscle Testing;
- NMMA=
- NG-monomethyl l-arginine;
- %FVC=
- percentage forced vital capacity;
- PRMT=
- protein arginine methyltransferase;
- SDMA=
- symmetric dimethyl l-arginine;
- TPPV=
- tracheostomy positive pressure ventilation
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received July 5, 2018.
- Accepted in final form December 17, 2018.
- © 2019 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)
Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here
Purchase
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.
Letters: Rapid online correspondence
REQUIREMENTS
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Dr. Jeffrey Allen and Dr. Nicholas Purcell
► Watch
Related Articles
- No related articles found.
Topics Discussed
Alert Me
Recommended articles
-
Articles
Subcutaneous IGF-1 is not beneficial in 2-year ALS trialE. J. Sorenson, A. J. Windbank, J. N. Mandrekar et al.Neurology, November 24, 2008 -
Article
Increased oxidative stress is related to disease severity in the ALS motor cortexA PET studyMasamichi Ikawa, Hidehiko Okazawa, Tetsuya Tsujikawa et al.Neurology, April 22, 2015 -
Articles
Clinical features that distinguish PLS, upper motor neuron–dominant ALS, and typical ALSP. H. Gordon, B. Cheng, I. B. Katz et al.Neurology, June 01, 2009 -
Article
A Prospective, Quantitative Study of the Natural History of Facioscapulohumeral Muscular Dystrophy (FSHD)Implications for Therapeutic Trials et al.Neurology, January 01, 1997