神经退行性变
星形胶质细胞
分泌物
神经保护
细胞内
细胞外
伴侣(临床)
细胞生物学
化学
生物
神经科学
生物化学
中枢神经系统
医学
疾病
病理
作者
Fangjia Yang,Paula Beltran-Lobo,Katherine Sung,Caoimhe Goldrick,Cara L. Croft,Agnes L. Nishimura,Erin C. Hedges,Farah Mahiddine,Claire Troakes,Todd E. Golde,Beatriz Gomez Perez‐Nievas,Diane P. Hanger,Wendy Noble,María Jiménez-Sánchez
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2024-03-20
卷期号:10 (12)
被引量:3
标识
DOI:10.1126/sciadv.adk9884
摘要
Molecular chaperones are protective in neurodegenerative diseases by preventing protein misfolding and aggregation, such as extracellular amyloid plaques and intracellular tau neurofibrillary tangles in Alzheimer’s disease (AD). In addition, AD is characterized by an increase in astrocyte reactivity. The chaperone HSPB1 has been proposed as a marker for reactive astrocytes; however, its astrocytic functions in neurodegeneration remain to be elucidated. Here, we identify that HSPB1 is secreted from astrocytes to exert non–cell-autonomous protective functions. We show that in human AD brain, HSPB1 levels increase in astrocytes that cluster around amyloid plaques, as well as in the adjacent extracellular space. Moreover, in conditions that mimic an inflammatory reactive response, astrocytes increase HSPB1 secretion. Concomitantly, astrocytes and neurons can uptake astrocyte-secreted HSPB1, which is accompanied by an attenuation of the inflammatory response in reactive astrocytes and reduced pathological tau inclusions. Our findings highlight a protective mechanism in disease conditions that encompasses the secretion of a chaperone typically regarded as intracellular.
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