Astrocytes Release HspB1 in Response to Amyloid-β Exposure in vitro

Nafar, Firoozeh; Williams, John B.; Mearow, Karen M.

doi:10.3233/jad-150317

Cited by 50 publications

(40 citation statements)

References 79 publications

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“…The results variate from reduced to significantly increased GFAP levels [65][66][67]. In addition, astrocytes express more HSP27 through stress or external stimuli [68]. In our model, no macrogliosis was detected at 21 days.…”

Section: No Glia Cell Responsementioning

confidence: 56%

Destructive Effect of Intravitreal Heat Shock Protein 27 Application on Retinal Ganglion Cells and Neurofilament

Grotegut¹,

Kuehn²,

Dick³

et al. 2020

IJMS

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Heat shock protein 27 (HSP27) is commonly involved in cellular stress. Increased levels of HSP27 as well as autoantibodies against this protein were previously detected in glaucoma patients. Moreover, systemic immunization with HSP27 induced glaucoma-like damage in rodents. Now, for the first time, the direct effects of an intravitreal HSP27 application were investigated. For this reason, HSP27 or phosphate buffered saline (PBS, controls) was applied intravitreally in rats (n = 12/group). The intraocular pressure (IOP) as well as the electroretinogram recordings were comparable in HSP27 and control eyes 21 days after the injection. However, significantly fewer retinal ganglion cells (RGCs) and amacrine cells were observed in the HSP27 group via immunohistochemistry and western blot analysis. The number of bipolar cells, on the other hand, was similar in both groups. Interestingly, a stronger neurofilament degeneration was observed in HSP27 optic nerves, while no differences were noted regarding the myelination state. In summary, intravitreal HSP27 injection led to an IOP-independent glaucoma-like damage. A degeneration of RGCs as well as their axons and amacrine cells was noted. This suggests that high levels of extracellular HSP27 could have a direct damaging effect on RGCs.

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Section: No Glia Cell Responsementioning

confidence: 56%

Destructive Effect of Intravitreal Heat Shock Protein 27 Application on Retinal Ganglion Cells and Neurofilament

Grotegut¹,

Kuehn²,

Dick³

et al. 2020

IJMS

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“…P2RX7 stimulates the release of autophagolysosomes/phagolysosomes from the microglia 49 . Astrocytes also release HSPB1 50 , and impaired clearance of HSPB1 decreases astroglial viability 23 . Thus, the increased HSPB1 protein level induced by P2rx7 deletion would be interpreted as the consequence from dysfunction of HSPB1 release from astrocytes.…”

Section: Discussionmentioning

confidence: 99%

P2RX7-MAPK1/2-SP1 axis inhibits MTOR independent HSPB1-mediated astroglial autophagy

Kim

Hyun

et al. 2018

Cell Death Dis

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Recently, we have reported that heat shock protein B1 (HSPB1) and purinergic receptor P2X7 (P2RX7) are involved in astroglial autophagy (clasmatodendrosis), following status epilepticus (SE). However, the underlying mechanisms of astroglial autophagy have not been completely established. In the present study, we found that the lacking of P2rx7 led to prolonged astroglial HSPB1 induction due to impaired mitogen-activated protein kinase 1/2 (MAPK1/2)-mediated specificity protein 1 (SP1) phosphorylation, following kainic acid-induced SE. Subsequently, the upregulated HSPB1 itself evoked ER stress and exerted protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1, AMPK1)/unc-51 such as autophagy activating kinase 1 (ULK1)- and AKT serine/threonine kinase 1 (AKT1)/glycogen synthase kinase 3 beta (GSK3B)/SH3-domain GRB2-like B1 (SH3GLB1)-mediated autophagic pathways, independent of mechanistic target of rapamycin (MTOR) activity in astrocytes. These findings provide a novel purinergic suppression mechanism to link chaperone expression to autophagy in astrocytes. Therefore, we suggest that P2RX7 may play an important role in the regulation of autophagy by the fine-tuning of HSPB1 expression.

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“…Astrocyte-derived exosomes also contain HSPB1; however, its role in relation to Huntington's disease has provided confusing results (Nafar et al 2016). On the one hand, a cross of the R6/2 mouse with an HSPB1 overexpression model did not lead to improvement of the R6/2 phenotype (Zourlidou et al 2007).…”

Section: Polyq Repeat Expansion-huntingtonmentioning

confidence: 99%

Small heat shock proteins in neurodegenerative diseases

Vendredy

Adriaenssens

Timmerman

2020

Cell Stress and Chaperones

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Small heat shock proteins are ubiquitously expressed chaperones, yet mutations in some of them cause tissue-specific diseases.Here, we will discuss how small heat shock proteins give rise to neurodegenerative disorders themselves while we will also highlight how these proteins can fulfil protective functions in neurodegenerative disorders caused by protein aggregation. The first half of this paper will be focused on how mutations in HSPB1, HSPB3, and HSPB8 are linked to inherited peripheral neuropathies like Charcot-Marie-Tooth (CMT) disease and distal hereditary motor neuropathy (dHMN). The second part of the paper will discuss how small heat shock proteins are linked to neurodegenerative disorders like Alzheimer's, Parkinson's, and Huntington's disease.

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Astrocytes Release HspB1 in Response to Amyloid-β Exposure in vitro

Cited by 50 publications

References 79 publications

Destructive Effect of Intravitreal Heat Shock Protein 27 Application on Retinal Ganglion Cells and Neurofilament

Destructive Effect of Intravitreal Heat Shock Protein 27 Application on Retinal Ganglion Cells and Neurofilament

P2RX7-MAPK1/2-SP1 axis inhibits MTOR independent HSPB1-mediated astroglial autophagy

Small heat shock proteins in neurodegenerative diseases

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