Reactive astrocytes secrete the chaperone HSPB1 to mediate neuroprotection

• DOI: 10.1126/sciadv.adk9884
• Publication Date: 2024-03-20T17:59:03Z
• Authors: Fangjia Yang; Paula Beltran-Lobo; Katherine Sung; Caoimhe Goldrick; Cara L. Croft; Agnes Nishimura; Erin Hedges; Farah Mahiddine; Claire Troakes; Todd E. Golde; Beatriz G. Perez-...; Diane P. Hanger; Wendy Noble; Maria Jimenez-San...
• Keywords: Chaperone (clinical)

Molecular chaperones are protective in neurodegenerative diseases by preventing protein misfolding and aggregation, such as extracellular amyloid plaques intracellular tau neurofibrillary tangles Alzheimer's disease (AD). In addition, AD is characterized an increase astrocyte reactivity. The chaperone HSPB1 has been proposed a marker for reactive astrocytes; however, its astrocytic functions neurodegeneration remain to be elucidated. Here, we identify that secreted from astrocytes exert non-cell-autonomous functions. We show human brain, levels cluster around plaques, well the adjacent space. Moreover, conditions mimic inflammatory response, secretion. Concomitantly, neurons can uptake astrocyte-secreted HSPB1, which accompanied attenuation of response reduced pathological inclusions. Our findings highlight mechanism encompasses secretion typically regarded intracellular.