SEARCHNARRATIVE_REVIEWneurology, preclinical research

narrative_review·neurology, preclinical research, biomedical research·PMC10011405

Astrocyte adaptation in Alzheimer’s disease: a focus on astrocytic P2X 7 R

Essays in Biochemistry · 6 authors, 5 centres

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This narrative review discusses the role of astrocytes and the purinergic receptor P2X7R in Alzheimer's disease (AD).

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This narrative review discusses the role of astrocytes and the purinergic receptor P2X7R in Alzheimer's disease (AD). Animal studies in mouse models of amyloidosis and tauopathy indicate that P2X7R antagonism or deletion can improve cognitive and synaptic impairments.

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narrative_review

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neurology

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ORIGINAL PAPER

PMC10011405

Astrocyte adaptation in Alzheimer’s disease: a focus on astrocytic P2X 7 R

Essays in Biochemistry

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ABSTRACT

Abstract Astrocytes are key homeostatic and defensive cells of the central nervous system (CNS). They undertake numerous functions during development and in adulthood to support and protect the brain through finely regulated communication with other cellular elements of the nervous tissue. In Alzheimer’s disease (AD), astrocytes undergo heterogeneous morphological, molecular and functional alterations represented by reactive remodelling, asthenia and loss of function. Reactive astrocytes closely associate with amyloid β (Aβ) plaques and neurofibrillary tangles in advanced AD. The specific contribution of astrocytes to AD could potentially evolve along the disease process and includes alterations in their signalling, interactions with pathological protein aggregates, metabolic and synaptic impairments. In this review, we focus on the purinergic receptor, P2X 7 R, and discuss the evidence that P2X 7 R activation contributes to altered astrocyte functions in AD. Expression of P2X 7 R is increased in AD brain relative to non-demented controls, and animal studies have shown that P2X 7 R antagonism improves cognitive and synaptic impairments in models of amyloidosis and tauopathy. While P2X 7 R activation can induce inflammatory signalling pathways, particularly in microglia, we focus here specifically on the contributions of astrocytic P2X 7 R to synaptic changes and protein aggregate clearance in AD, highlighting cell-specific roles of this purinoceptor activation that could be targeted to slow disease progression.

CITATION EXPORT

Paula Beltran-Lobo, Matthew J. Reid, Maria Jimenez-Sanchez et al.. Astrocyte adaptation in Alzheimer’s disease: a focus on astrocytic P2X7R. Essays in Biochemistry. (2023). https://doi.org/10.1042/EBC20220079

AUTHORS

6 · 5 CENTRES

Paula Beltran-Lobo, Matthew J. Reid, Maria Jimenez-Sanchez, Alexei Verkhratsky, Beatriz G. Perez-Nievas, Wendy Noble

1Department of Basic and Clinical Neuroscience, King’s College London, Institute of Psychiatry, Psychology and Neuroscience, 5 Cutcombe Road, London, SE5 9RX, U.K.
2Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, U.K.
3Achucarro Center for Neuroscience, IKERBASQUE, 48011 Bilbao, Spain
4Department of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China
5Department of Stem Cell Biology, State Research Institute Centre for Innovative Medicine, LT-01102, Vilnius, Lithuania

EDITOR / REVIEWER

Juan P Bolaños