Calcium signaling pathways mediating synaptic potentiation triggered by amyotrophic lateral sclerosis IgG in motor nerve terminals

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Mario R PaganiOsvaldo D Uchitel

Abstract

Sporadic amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects particularly motoneurons. Several pieces of evidence suggested the involvement of autoimmune mechanisms mediated by antibodies in ALS. However, the significance of those antibodies in the disease and the underlying mechanisms are unknown. Here we showed that IgG purified from a group of sporadic ALS patients, but not familial ALS patients, specifically interact with the presynaptic membrane of motoneurons through an antigen-antibody interaction and modulated synaptic transmission. Immunoreactivity against nerve terminals showed strong correlation with synaptic modulation ability. In addition, several controls have ruled out the possibility for this synaptic modulation to be mediated through proteases or nonspecific effects. Effective IgG potentiated both spontaneous and asynchronous transmitter release. Application of pharmacological inhibitors suggested that activation of this increased release required a nonconstitutive Ca2+ influx through N-type (Cav2.2) channels and phospholipase C activity and that activation of IP3 and ryanodine receptors were necessary to both activate and sustain the increased release. Consistent with the notion tha...Continue Reading

Citations

Aug 10, 2011·Neurology Research International·Mario Rafael PaganiOsvaldo Daniel Uchitel
Mar 26, 2010·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·R Scott DuncanPeter Koulen
Jun 21, 2014·BioMed Research International·Danijela BataveljicPavle Andjus
Jun 26, 2008·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Christen Shoesmith
Apr 9, 2016·Journal of Neuroinflammation·Nawal Bahia El IdrissiDirk Troost
Dec 25, 2012·Journal of Neurology, Neurosurgery, and Psychiatry·Steve VucicMatthew C Kiernan
Aug 23, 2016·Biochemical and Biophysical Research Communications·Roland PataiLászló Siklós
Mar 22, 2007·Muscle & Nerve·Clemens NeuschChristiane Schneider-Gold
Aug 12, 2016·Physiological Reviews·Michael J Berridge
Jun 13, 2019·International Journal of Molecular Sciences·Mehdi A J van den BosSteve Vucic
Dec 18, 2020·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Can CuiFang Fang
Jan 30, 2021·Neural Regeneration Research·Andrei N Tsentsevitsky, Alexey M Petrov

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.