Astrocyte adaptation in Alzheimer's disease: a focus on astrocytic P2X7R

被引:20
作者
Beltran-Lobo, Paula [1 ]
Reid, Matthew J. [1 ]
Jimenez-Sanchez, Maria [1 ]
Verkhratsky, Alexei [2 ,3 ,4 ,5 ]
Perez-Nievas, Beatriz G. [1 ]
Noble, Wendy [1 ]
机构
[1] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Basic & Clin Neurosci, 5 Cutcombe Rd, London SE5 9RX, England
[2] Univ Manchester, Fac Biol Med & Hlth, Manchester, England
[3] Achucarro Ctr Neurosci, IKERBASQUE, Bilbao 48011, Spain
[4] China Med Univ, Sch Forens Med, Dept Forens Analyt Toxicol, Shenyang, Peoples R China
[5] State Res Inst Ctr Innovat Med, Dept Stem Cell Biol, LT-01102 Vilnius, Lithuania
基金
英国医学研究理事会;
关键词
RECEPTOR-MEDIATED RELEASE; FIBRILLARY ACIDIC PROTEIN; TRANSGENIC MOUSE MODEL; LONG-TERM POTENTIATION; A-BETA CLEARANCE; P2X(7) RECEPTOR; D-SERINE; IN-VIVO; PHARMACOLOGICAL CHARACTERIZATION; EXTRACELLULAR ATP;
D O I
10.1042/EBC20220079
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 morpho-logical, molecular and functional alterations represented by reactive remodelling, asthenia and loss of function. Reactive astrocytes closely associate with amyloid (3 (A(3) 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, in-teractions with pathological protein aggregates, metabolic and synaptic impairments. In this review, we focus on the purinergic receptor, P2X7R, and discuss the evidence that P2X7R activation contributes to altered astrocyte functions in AD. Expression of P2X7R is increased in AD brain relative to non-demented controls, and animal studies have shown that P2X7R antagonism improves cognitive and synaptic impairments in models of amyloidosis and tauopathy. While P2X7R activation can induce inflammatory signalling pathways, particu-larly in microglia, we focus here specifically on the contributions of astrocytic P2X7R 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.
引用
收藏
页码:119 / 130
页数:12
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