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P1‐195: OVERPRODUCTION OF DIFFERENT β‐AMYLOID PEPTIDES IN RETINA, OPTIC NERVE AND VISUAL CORTEX IN HEALTHY AGING AND ALZHEIMER'S DISEASE
Author(s) -
Hernández-Zimbrón Luis Fernando,
Martínez-Hernández Uriel,
Pérez-Hernández Montserrat,
Torres-Romero Abigail,
Gonzalez-Salinas Roberto,
Quiroz-Mercado Hugo
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.199
Subject(s) - senile plaques , retina , neurodegeneration , visual cortex , amyloid (mycology) , alzheimer's disease , bace1 as , amyloid precursor protein , p3 peptide , adam10 , cortex (anatomy) , retinal , extracellular , chemistry , endocrinology , medicine , pathology , biology , neuroscience , enzyme , biochemistry , disease , disintegrin , metalloproteinase
(CsA). Patch-clamp results suggest that Ab-suppression of Kv1.1 involves both PP2B-dephosphorylation and direct protein-protein interaction of Ab with Kv1.1 channel subunits. Exposure of inside-out single Kv1.1 in ripped-off oocyte patches to application of purified, catalytically-active PP2B produced gradual reductions in p(open), followed by abrupt disappearance of Kv1.1 activity. Application of Ab to the intracellular face of Kv1.1 channels also produced dramatic reductions in p(open). Additional results indicate that 2 mM of Ab(25-35) suppressed Kv1.1 currents by w40%. Using “tip-dip” artificial membrane methods, 1 mM Ab(25-35) exposure eliminated Kv1.1 channel activity when applied to the intracellular face. Conclusions: The toxic Ab fragments (1-42) and (25-35) suppress the voltage-gated potassium channel, Kv1.1. Suppression of Kv1.1 and related K channels presynaptically could lead to larger and longer action potentials, allowing more influx of Ca, increased release of glutamate, and possibly the beginning of a disruption of Ca homeostasis. Postsynaptically, the increased glutamate release, through activation of AMPA and NMDA receptors, may contribute to excitotoxicity.