Amyloid Beta Peptides Block New Synapse Assembly by Nogo Receptor-Mediated Inhibition of T-Type Calcium Channels.

Abstract:

:Compelling evidence links amyloid beta (Aβ) peptide accumulation in the brains of Alzheimer's disease (AD) patients with the emergence of learning and memory deficits, yet a clear understanding of the events that drive this synaptic pathology are lacking. We present evidence that neurons exposed to Aβ are unable to form new synapses, resulting in learning deficits in vivo. We demonstrate the Nogo receptor family (NgR1-3) acts as Aβ receptors mediating an inhibition of synapse assembly, plasticity, and learning. Live imaging studies reveal Aβ activates NgRs on the dendritic shaft of neurons, triggering an inhibition of calcium signaling. We define T-type calcium channels as a target of Aβ-NgR signaling, mediating Aβ's inhibitory effects on calcium, synapse assembly, plasticity, and learning. These studies highlight deficits in new synapse assembly as a potential initiator of cognitive pathology in AD, and pinpoint calcium dysregulation mediated by NgRs and T-type channels as key components. VIDEO ABSTRACT.

journal_name

Neuron

journal_title

Neuron

authors

Zhao Y,Sivaji S,Chiang MC,Ali H,Zukowski M,Ali S,Kennedy B,Sklyar A,Cheng A,Guo Z,Reed AK,Kodali R,Borowski J,Frost G,Beukema P,Wills ZP

doi

10.1016/j.neuron.2017.09.041

subject

Has Abstract

pub_date

2017-10-11 00:00:00

pages

355-372.e6

issue

2

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(17)30910-8

journal_volume

96

pub_type

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