Amyloid Beta Peptides Block New Synapse Assembly by Nogo Receptor Mediated Inhibition of T-Type Calcium Channels
| Autor: | Alexander K. Reed, Zachary P. Wills, Sivaprakash Sivaji, Alice Cheng, Michael C. Chiang, Haadi Ali, Sareen Ali, Alex Sklyar, Patrick Beukema, Jennifer Borowski, Zihan Guo, Yanjun Zhao, Georgia R. Frost, Ravindra Kodali, Bryan Kennedy, Monica Zukowski |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Nogo Receptors Amyloid beta chemistry.chemical_element Mice Transgenic CHO Cells Calcium Inhibitory postsynaptic potential Article 03 medical and health sciences Calcium Channels T-Type Mice 0302 clinical medicine Cricetulus Organ Culture Techniques Cricetinae Animals Humans Rats Long-Evans Calcium Signaling Receptor Cells Cultured Calcium signaling Mice Knockout Amyloid beta-Peptides biology Voltage-dependent calcium channel Synapse assembly General Neuroscience T-type calcium channel Calcium Channel Blockers Peptide Fragments Rats 030104 developmental biology HEK293 Cells chemistry Synapses biology.protein Female Neuroscience 030217 neurology & neurosurgery |
| Popis: | Summary 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 |
| Databáze: | OpenAIRE |
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