INIBIBB   05455
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BAHIA BLANCA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Effects of beta amyloid on alpha7 receptor function.
Autor/es:
MAÍAS LASALA; JEREMÍAS CORRADI; CECILIA BOUZAT
Lugar:
Sierra de la Ventana
Reunión:
Congreso; XLIII Reunión Anual SAB 2014; 2014
Institución organizadora:
Sociedad argentina de biofísica
Resumen:
Alzheimer?s disease (AD) is the most common form of
dementia in elderly people that produces a severe impairment in mental function,
with profound effects on learning and memory. The beta amyloid peptide (bA)
plays an important role in AD development. Several studies have shown that bA
can affect cholinergic signaling in the brain but the specific mechanism is
still obscure. Of the nicotinic acetylcholine receptors at risk, the most
critical may be those containing the alpha7 subunit, because they are widespread,
have a high relative permeability to calcium, and regulate numerous cellular
events in the nervous system. Here we explore the effect of bA1-40 on the human
alpha7 nicotinic receptors at the single-channel level. We observe that nanomolar
concentrations of beta amyloid peptides block human alpha7 receptors. In the
presence of 100mM ACh combined
with the positive allosteric modulator PNU, single-channel episodes appear as
openings of ~200ms grouped in
long clusters of ~3s and high open
probability (>0.9). In the presence of bA there is a clear reduction in
open- and cluster-duration (~4-fold and
2-fold, respectively at 500nM of bA). Our results demonstrate that bA antagonizes
the human alpha7 receptor by at least two different mechanisms, one that produces
reduction in the open duration, probably acting as an open channel blocker, and
another that reduces cluster duration, which is compatible with slow block or
increased desensitization. Understanding the actual mechanism that leads to the
neuronal damage would help to design more effective and specific treatments for
AD patients.