Title:The Role of Ca2+ Permeable AMPA Receptors in Neurodegeneration,
Neurotoxicity, and Neuroinflammation
Volume: 22
Issue: 5
Author(s): José Afonso Corrêa da Silva and Nadja Schröder*
Affiliation:
- Department of Physiology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre,
Brazil
- National Institute of Science and Technology for Translational Medicine (INCT-TM), Conselho Nacional de
Desenvolvimento Cientifico e Tecnológico (CNPq), Brasília, Brazil
Keywords:
AMPA receptors, calcium-permeable AMPA receptors (CP-AMPAR), neurodegenerative diseases, calcium, pharmacological target, neurotoxicity.
Abstract: It is believed that degenerative conditions that give rise to neurological diseases may share
an abnormal influx of Ca2+, mainly through glutamate receptors. Current research on the glutamatergic
system indicates that the N-methyl-D-aspartate receptor (NMDAR) is not the only receptor permeable
to Ca2+. Under certain conditions, α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors
(AMPARs) are able to rapidly and potently mediate a neurotoxic Ca2+ influx. AMPARs are encoded
by four genes designated GluR 1-4. The presence of the edited GluA2 subunit makes the heteromeric
AMPAR impermeable to Ca2+ (CI-AMPAR's). On the other hand, the lack of GluA2 or disruptions in
its post-translational editing result in Ca2+-permeable AMPA receptors (CP-AMPARs). In addition to
triggering behavioral changes, the increase in CP-AMPARs is documented in several neurodegenerative,
neuroinflammatory and neurotoxic conditions, demonstrating that AMPAR changes may play a
role in the emergence and evolution of pathological conditions of the central nervous system (CNS).
Seeking to better understand how CP-AMPARs influence CNS neuropathology, and how it may serve
as a pharmacological target for future molecules, in this article, we summarize and discuss studies investigating
changes in the composition of AMPARs and their cellular and molecular effects, to improve
the understanding of the therapeutic potential of the CP-AMPAR in neurodegenerative, neurotoxic
and neuroinflammatory diseases.