UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Insight into the role of phosphatidylserine in complement-mediated synapse loss in Alzheimer's disease.

Sokolova, D; Childs, T; Hong, S; (2021) Insight into the role of phosphatidylserine in complement-mediated synapse loss in Alzheimer's disease. Faculty Opinions , 10 , Article 19. 10.12703/r. Green open access

[img]
Preview
Text
article.pdf - Published version

Download (3MB) | Preview

Abstract

The innate immune system plays an integral role in the brain. Synaptic pruning, a fundamental process in developmental circuit refinement, is partially mediated by neuroimmune signalling at the synapse. In particular, microglia, the major tissue-resident macrophages of the brain, and the classical complement cascade, an innate immune pathway that aids in the clearance of unwanted material, have been implicated in mediating synapse elimination. Emerging data suggest that improper signalling of the innate immune pathway at the synapse leads to pathological synapse loss in age-related neurodegenerative diseases, including Alzheimer's disease. Now the key questions are whether synapses are targeted by complement and, if so, which synapses are vulnerable to elimination. Here, we review recent work implicating C1q, the initiator of the classical complement cascade, and surrounding glia as mediators of synapse loss. We examine how synapses could undergo apoptosis-like pathways in the Alzheimer brain, which may lead to the externalisation of phosphatidylserine on synapses. Finally, we discuss potential roles for microglia and astrocytes in this 'synaptic apoptosis'. Critical insight into neuroimmune regulatory pathways on synapses will be key to developing effective targets against pathological synapse loss in dementia.

Type: Article
Title: Insight into the role of phosphatidylserine in complement-mediated synapse loss in Alzheimer's disease.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.12703/r
Publisher version: https://doi.org/10.12703/r/10-19
Language: English
Additional information: © 2021 Hong S et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Alzheimer’s disease, MFG-E8, TAM, TREM2, astrocyte, caspase-3, classical complement cascade, microglia, mitochondrial dysfunction, phosphatidylserine, synapse loss, synaptosis
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10125411
Downloads since deposit
3Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item