The C9ORF72 Protein as a Suppressor of Autoimmunity

There are many chronic illnesses that are referred to as autoimmune diseases such as multiple sclerosis, amyotrophic lateral sclerosis (ALS) and pemphigus vulgaris for example; the etiology of these diseases originates from the patient’s immune system attacking normal tissue.   

ALS is a disease that presents as a progressive degeneration of the normal function of motor neurons resulting in paralysis and death.  It has been shown that mutations in the C9ORF72 gene are commonly found in ALS and frontotemporal dementia.  This gene is located on the short arm of chromosome 9 in humans.  This gene contains the information for the production of the C9orf72 protein.  Furthermore, in animal model studies using the mouse, it has been found that mutations in this gene result in Autoimmune-like symptoms.  Transplantation of normal murine bone marrow positively impacted diseased mice with this mutation and bone marrow transplantation of diseased mice into normal animals alternatively resulted in symptoms of autoimmunity.  These latter results led investigators to suspect that the C9orf72 gene is normally active in hematopoietic cells – cells residing in the bone marrow that produce circulating blood cells - in suppressing autoimmunity.

Recent findings have clearly established that mice that harbor mutations in the C9orf72 gene that result in the loss of function of the C9orf72 protein gene product develop the following symptoms –

• splenomegaly – enlarged spleen
• neutrophilia – increased population of neutrophils in the circulation
• thrombocytopenia – decreased numbers of platelets
• increased expression of inflammatory cytokines
• severe autoimmunity.

These diseased animal suffer a high mortality rate.

These data represent strong evidence that the C9ORF72 gene plays a very important role in the suppression of autoimmunity and may prove to be of future therapeutic value.

What Will be Our Legacy?

The essential questions I would like to pose are the following-

• Are we prepared to leave as our legacy not only to future generations of humans, but also the future of our fellow creatures a world whose living populations will be severely decimated by the onslaught of climate change brought on by human activity?
• Are we prepared to jeopardize the quality of life and security of future generations of humanity on planet Earth so that we can maintain our privileged and comfortable lifestyles based upon a patent disregard for the environmental degradation that we necessarily impose upon our planet?

These questions are no longer simply philosophical in nature.  The current data is clear that we are in the midst of a major change in the global environment caused primarily by human activity.  The following statement was made within the Smithsonian Museums website – Smithsonian.com – “According to the International Union of Geological Sciences (IUGS), the professional organization in charge of defining Earth’s time scale, we are officially in the Holocene (“entirely recent”) epoch, which began 11,700 years ago after the last major ice age.

“But that label is outdated, some experts say. They argue for “Anthropocene”—from anthropo, for “man,” and cene, for “new”—because human-kind has caused mass extinctions of plant and animal species, polluted the oceans and altered the atmosphere, among other lasting impacts.”

Humanity’s response, within the 21^st century, to this real crisis will determine the future that awaits the living world.  Of course, the earth has been through at least five major mass extinctions in its long geological history and will certainly survive another.  The kind of adjustments involved, however, require long stretches of time involving many thousands if not millions of years.  We do not have the luxury of waiting.  The future of the natural environment depends upon what we do, or what we fail to do now.