Original Contributions |

Differential Involvement of Optineurin in Amyotrophic Lateral Sclerosis With or Without SOD1 Mutations

Han-Xiang Deng, MD, PhD; Eileen H. Bigio, MD; Hong Zhai, MS; Faisal Fecto, MD; Kaouther Ajroud, PhD; Yong Shi, MD, PhD; Jianhua Yan, MD, PhD; Manjari Mishra, PhD; Senda Ajroud-Driss, MD; Scott Heller, MD; Robert Sufit, MD; Nailah Siddique, RN, MSN; Enrico Mugnaini, MD; Teepu Siddique, MD
Arch Neurol. 2011;68(8):1057-1061. doi:10.1001/archneurol.2011.178.
Text Size: A A A
Published online

Background Mutations in optineurin have recently been linked to amyotrophic lateral sclerosis (ALS).

Objective To determine whether optineurin-positive skeinlike inclusions are a common pathologic feature in ALS, including SOD1 -linked ALS.

Design Clinical case series.

Setting Academic referral center.

Subjects We analyzed spinal cord sections from 46 clinically and pathologically diagnosed ALS cases and ALS transgenic mouse models overexpressing ALS-linked SOD1 mutations G93A or L126Z.

Results We observed optineurin-immunoreactive skeinlike inclusions in all the sporadic ALS and familial ALS cases without SOD1 mutation, but not in cases with SOD1 mutations or in transgenic mice overexpressing the ALS-linked SOD1 mutations G93A or L126Z.

Conclusion The data from this study provide evidence that optineurin is involved in the pathogenesis of sporadic ALS and non- SOD1 familial ALS, thus supporting the hypothesis that these forms of ALS share a pathway that is distinct from that of SOD1 -linked ALS.

Figures in this Article

Sign In to Access Full Content

Don't have Access?

Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more

Subscribe for full-text access to content from 1998 forward and a host of useful features

Activate your current subscription (AMA members and current subscribers)

Purchase Online Access to this article for 24 hours


Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Optineurin (OPTN)-immunoreactive inclusions in amyotrophic lateral sclerosis (ALS). Representative OPTN-immunoreactive inclusions were detected by antibody C-term in sporadic ALS (SALS) (A-C and F) and non- SOD1 familial ALS (FALS) (D and E). The typical skeinlike inclusions in soma and neurites are shown by small arrows and arrowheads, respectively. Some inclusions appeared to be compact (large arrowhead in panel F). Representative Bunina bodies (large arrow in panel G) stained with hematoxylin and eosin (H&E) were destained, then restained with OPTN antibody and were negative for OPTN (H).

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Immunoreactivity of optineurin in ubiquitin-positive inclusions in sporadic amyotrophic lateral sclerosis (SALS) cases, SOD1 -linked ALS, and SOD1 transgenic (Tg) mice. Confocal microscopy was performed using antibodies to optineurin (green) and ubiquitin (red) on the spinal cord sections from ALS cases and Tg mice. Representative images show that the ubiquitin-positive inclusions are optineurin-positive in SALS cases (A-C), but negative in SOD1-G85R (D-F) and SOD1-A4V (G-I), as well as in ALS Tg mice overexpressing SOD1-G93A (J-L) or SOD1-L126Z (M-O). Representative optineurin-positive skeinlike inclusions in an SALS case are indicated by arrows in panel A. The ubiquitin-positive inclusions in soma and neurites are indicated by arrows and arrowheads, respectively, in panels B, E, H, K, and N.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 3. Schematic model depicting 2 parallel pathways involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). TDP-43, FUS, and optineurin are components of pathologic inclusions in sporadic ALS (SALS) and SOD1 -negative familial ALS (FALS). SOD1-positive inclusions are exclusively present in SOD1 -linked FALS. Ubiquitin and p62 may represent a common pathway involved in the formation of skeinlike inclusions, eventually leading to motor neuron degeneration.




Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment


Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Topics