Analysis of Post-Translational Modifications of a Critical Protein Implicated in Amyotrophic Lateral Sclerosis

Study Purpose:

The purpose of this research study is to discover and quantitate the differences in post-translational modifications found in the Cu, Zn superoxide dismutase (SOD1) of patients with amyotrophic lateral sclerosis (ALS) as compared to healthy individuals. SOD1 is a known genetic cause of ALS. With certain mutations, SOD1 gains a toxic function which leads to motor neuron death.

Study Status:

Not recruiting



Study Type:


Type of Intervention:


Intervention Name:






Study Chair(s)/Principal Investigator(s):

Chafic Karam, MD, University of North Carolina, Chapel Hill, Nikolay V Dokholyan, PhD, UNC ID:


Neals Affiliated?


Coordinating Center Contact Information

UNC Neurology ALS Clinic

Chapel Hill, North Carolina, 27599 United States

Full Study Summary:

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease in which mutations in human Cu, Zn Superoxide Dismutase (SOD1) have been identified as a cause of familial ALS (FALS) cases.1-2 It has been shown that mutant SOD1 develops a novel toxic function through experiments demonstrating that many disease mutants maintain enzymatic activity, SOD1-null mice do not exhibit ALS symptoms, and co-expressed wild type protein does not rescue the disease-state.7-11 The majority of cases, however, are not caused directly by mutations of SOD1, instead being caused by a poorly understood interplay of several genes as well as environmental factors, which is often referred to as sporadic ALS (SALS).3 It has been found that FALS and SALS share similar pathology. 4-6 The hSOD1 protein aggregates characteristic of FALS have also been found in SALS patients, furthering the evidence that hSOD1 has an important role in the etiology of ALS in sporadic ALS patients.16-19 The exact mechanism of SOD1-associated toxicity has not yet been elucidated though many disease mutants have been shown to destabilize the SOD1 dimer. In this study we aim to compare the levels of SOD1 post-tra slational modifications in ALS patients to levels in healthy donors and to determine if there are distinct patterns of protein glutathionylation or phosphorylation. Our overall goal is to elucidate a direct mechanism of toxicity in SALS as well as identify potentially critical triggers

Study Sponsor:

University of North Carolina, Chapel Hill

Estimated Enrollment:


Estimated Study Start Date:

08 / 01 / 2014

Estimated Study Completion Date:

10 / 16 / 2018

Posting Last Modified Date:

10 / 17 / 2018

Date Study Added to

08 / 29 / 2014

Minimum Age:

18 Years

Maximum Age:

99 Years

Inclusion Criteria:

- SALS patients

- SOD1 associated FALS patients

- Healthy control

Exclusion Criteria: none

UNC Neurology ALS clinic

Chapel Hill, North Carolina 27599
United States