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Comment
. 2023 Aug 2;111(15):2277-2279.
doi: 10.1016/j.neuron.2023.06.014.

Timing matters: A protective role of astrocyte reactivity in neurodegeneration

Daniela Rojo  1 , Erin M Gibson  2
Affiliations
Comment

Timing matters: A protective role of astrocyte reactivity in neurodegeneration

Daniela Rojo et al. Neuron. .

Abstract

Sheehan and Nadarajah et al.1 identified that Bmal1 loss from astrocytes induces the expression of BAG3, a macroautophagy chaperone enriched in Alzheimer's disease patients and in disease-associated astrocytes, enhancing the phagocytosis of misfolded proteins and preventing tau and alpha-synuclein pathologies.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Figures

Figure 1.
Figure 1.. The BMAL1-BAG3 axis is involved in the regulation of protein clearance in the brain
In mouse models for Alzheimer’s and Parkinson’s disease, the deletion of the circadian regulator BMAL1 induces a characteristic phenotype of astrocyte reactivity that increases the expression of the chaperone BAG3, leading to the clearance of misfolded protein aggregates tau and αSyn and reducing the pathology associated. In humans with Alzheimer’s and Parkinson’s disease, BAG3 is also linked to symptomatic dementia and its expression is increased in disease-associated astrocytes in late stages of the disease. Moreover, variations in a region of open chromatin in astrocytes increases the risk of developing Parkinson’s disease. Made with BioRender.com.
See this image and copyright information in PMC

Comment on

  • An astrocyte BMAL1-BAG3 axis protects against alpha-synuclein and tau pathology.
    Sheehan PW, Nadarajah CJ, Kanan MF, Patterson JN, Novotny B, Lawrence JH, King MW, Brase L, Inman CE, Yuede CM, Lee J, Patel TK, Harari O, Benitez BA, Davis AA, Musiek ES. Sheehan PW, et al. Neuron. 2023 Aug 2;111(15):2383-2398.e7. doi: 10.1016/j.neuron.2023.05.006. Epub 2023 Jun 13. Neuron. 2023. PMID: 37315555 Free PMC article.

References

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