Promotion of axon regeneration and inhibition of astrocyte activation by alpha A-crystallin on crushed optic nerve

Shao, Wei-Yang; Liu, Xiao; Gu, Xianliang; Xiao, Ying; Wu, Nan; Xu, Haiwei; Wang, Yi

doi:10.18240/ijo.2016.07.04

Cited by 5 publications

(3 citation statements)

References 45 publications

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“…An important limitation of these studies is that the researchers studied co-purified aggregates containing αA- and αB-crystallins, precluding at this point a clear understanding of the relative contribution of each individual chaperone. Starting to clarify the individual roles of αA- and αB-crystallin, a recent study reported an association between αA-crystallin, inhibition of astrocyte activation, and axon elongation following optic nerve crush ( Shao et al, 2016 ). On the other hand, cell culture experiments using hippocampal neurons have shown that αB-crystallin regulates dendritic complexity, and does so in a phosphorylation-dependent manner ( Bartelt-Kirbach et al, 2016 ).…”

Section: Heat Shock Proteins Regulate Neuronal and Glial Cell Growthmentioning

confidence: 99%

Heat Shock Proteins Regulatory Role in Neurodevelopment

2018

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Heat shock proteins (Hsps) are a large family of molecular chaperones that are well-known for their roles in protein maturation, re-folding and degradation. While some Hsps are constitutively expressed in certain regions, others are rapidly upregulated in the presence of stressful stimuli. Numerous stressors, including hyperthermia and hypoxia, can induce the expression of Hsps, which, in turn, interact with client proteins and co-chaperones to regulate cell growth and survival. Such interactions must be tightly regulated, especially at critical points during embryonic and postnatal development. Hsps exhibit specific patterns of expression consistent with a spatio-temporally regulated role in neurodevelopment. There is also growing evidence that Hsps may promote or inhibit neurodevelopment through specific pathways regulating cell differentiation, neurite outgrowth, cell migration, or angiogenesis. This review will examine the regulatory role that these individual chaperones may play in neurodevelopment, and will focus specifically on the signaling pathways involved in the maturation of neuronal and glial cells as well as the underlying vascular network.

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Section: Heat Shock Proteins Regulate Neuronal and Glial Cell Growthmentioning

confidence: 99%

Heat Shock Proteins Regulatory Role in Neurodevelopment

2018

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“…Similarly, exogenous supplementation of αA-crystallin via intravitreal injections was associated with significantly decreased levels of GFAP in both the retina and the crush site following the third day of optic nerve crush injury and induced astrocytes architecture remodeling at the crush site ( Piri et al, 2016 ). In the increased intraocular pressure model, intravitreal injection of αB-crystallin was also able to increase RGCs survival and function, as measured by functional photopic electroretinogram, retinal nerve fiber layer thickness, and RGC counts ( Shao et al, 2016 ). Another study has reported the enhanced rate of survival in the axotomized axons beyond the crush site after a single intravitreal administration of α-crystallin at the time of axotomy ( Anders et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Evidence for Paracrine Protective Role of Exogenous αA-Crystallin in Retinal Ganglion Cells

Nath

Sluzala

Phadte

et al. 2022

eNeuro

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Expression and secretion of neurotrophic factors have long been known as a key mechanism of neuroglial interaction in the central nervous system. In addition, several other intrinsic neuroprotective pathways have been described, including those involving small heat shock proteins such as α-crystallins. While initially considered as a purely intracellular mechanism, both αA-crystallins and αB-crystallins have been recently reported to be secreted by glial cells. While an anti-apoptotic effect of such secreted αA-crystallin has been suggested, its regulation and protective potential remain unclear. We recently identified residue threonine 148 (T148) and its phosphorylation as a critical regulator of αA-crystallin intrinsic neuroprotective function. In the current study, we explored how mutation of this residue affected αA-crystallin chaperone function, secretion, and paracrine protective function using primary glial and neuronal cells. After demonstrating the paracrine protective effect of αA-crystallins secreted by primary Müller glial cells (MGCs), we purified and characterized recombinant αA-crystallin proteins mutated on the T148 regulatory residue. Characterization of the biochemical properties of these mutants revealed an increased chaperone activity of the phosphomimetic T148D mutant. Consistent with this observation, we also show that exogeneous supplementation of the phosphomimetic T148D mutant protein protected primary retinal neurons from metabolic stress despite similar cellular uptake. In contrast, the nonphosphorylatable mutant was completely ineffective. Altogether, our study demonstrates the paracrine role of αA-crystallin in the central nervous system as well as the therapeutic potential of functionally enhanced αA-crystallin recombinant proteins to prevent metabolic-stress induced neurodegeneration.

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“…In further experiments in this study, α-crystallin was shown to have a scavenging ability toward sulfur and nitrogen oxides. Inhibition of astrocyte activation was also demonstrated in an optic nerve crush model by intravitreal application of αA-crystallin [ 125 ]. The mechanism of neuroprotective action is not fully understood; however, recent studies showed that phosphorylation of tyrosine 148 mediates protective properties on αA-crystallin in experimental diabetic models [ 126 ].…”

Section: Therapeutical Approaches For Future Glaucoma Therapymentioning

confidence: 99%

Antibody and Protein Profiles in Glaucoma: Screening of Biomarkers and Identification of Signaling Pathways

Auler

Tonner

Pfeiffer

et al. 2021

Biology

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Glaucoma represents a group of chronic neurodegenerative diseases, constituting the second leading cause of blindness worldwide. To date, chronically elevated intraocular pressure has been identified as the main risk factor and the only treatable symptom. However, there is increasing evidence in the recent literature that IOP-independent molecular mechanisms also play an important role in the progression of the disease. In recent years, it has become increasingly clear that glaucoma has an autoimmune component. The main focus nowadays is elucidating glaucoma pathogenesis, finding early diagnostic options and new therapeutic approaches. This review article summarizes the impact of different antibodies and proteins associated with glaucoma that can be detected for example by microarray and mass spectrometric analyzes, which (i) provide information about expression profiles and associated molecular signaling pathways, (ii) can possibly be used as a diagnostic tool in future and, (iii) can identify possible targets for therapeutic approaches.

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Promotion of axon regeneration and inhibition of astrocyte activation by alpha A-crystallin on crushed optic nerve

Abstract: Our results suggest α-crystallin promotes the axon regeneration of RGCs and suppresses the activation of astrocytes.

Cited by 5 publications

References 45 publications

Heat Shock Proteins Regulatory Role in Neurodevelopment

Heat Shock Proteins Regulatory Role in Neurodevelopment

Evidence for Paracrine Protective Role of Exogenous αA-Crystallin in Retinal Ganglion Cells

Antibody and Protein Profiles in Glaucoma: Screening of Biomarkers and Identification of Signaling Pathways

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