Neurogranin restores amyloid β-mediated synaptic transmission and long-term potentiation deficits. Exp Neurol 2016 Mar;277:115-123
Date
01/02/2016Pubmed ID
26721336DOI
10.1016/j.expneurol.2015.12.013Scopus ID
2-s2.0-84952802048 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
Amyloid β (Aβ) is widely considered one of the early causes of cognitive deficits observed in Alzheimer's disease. Many of the deficits caused by Aβ are attributed to its disruption of synaptic function represented by its blockade of long-term potentiation (LTP) and its induction of synaptic depression. Identifying pathways that reverse these synaptic deficits may open the door to new therapeutic targets. In this study, we explored the possibility that Neurogranin (Ng)-a postsynaptic calmodulin (CaM) targeting protein that enhances synaptic function-may rescue Aβ-mediated deficits in synaptic function. Our results show that Ng is able to reverse synaptic depression and LTP deficits induced by Aβ. Furthermore, Ng's restoration of synaptic transmission is through the insertion of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPARs). These restorative effects of Ng are dependent on the interaction of Ng and CaM and CaM-dependent activation of CaMKII. Overall, this study identifies a novel mechanism to rescue synaptic deficits induced by Aβ oligomers. It also suggests Ng and CaM signaling as potential therapeutic targets for Alzheimer's disease as well as important tools to further explore the pathophysiology underlying the disease.
Author List
Kaleka KS, Gerges NZAuthor
Nashaat Gerges PhD Chair, Professor in the School of Pharmacy Administration department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amyloid beta-PeptidesAmyloid beta-Protein Precursor
Animals
Animals, Newborn
Excitatory Amino Acid Antagonists
Excitatory Postsynaptic Potentials
Hippocampus
Humans
In Vitro Techniques
Long-Term Potentiation
Mutagenesis
Mutation
Nerve Net
Neurogranin
Neurons
Rats
Rats, Sprague-Dawley
Sodium Channel Blockers
Synaptic Transmission
Tetrodotoxin
