Role of crystallins in ocular neuroprotection and axonal regeneration

Thanos, Solon; Böhm, Michael; Hörste, Melissa Meyer zu; Prokosch‐Willing, Verena; Hennig, Maren; Bauer, Dirk; Heiligenhaus, A.

doi:10.1016/j.preteyeres.2014.06.004

Cited by 62 publications

(53 citation statements)

References 147 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While there are many reports for the non-lenticular presence and functions of α-crystallins, and also some members of the β-crystallin family, particularly in the retina, the roles of γ-crystallins are just getting to be understood [104,105]. Based on the idea that γS-crystallin is an outlier of the γ family, with some characteristics that appear more likely to retain non-lens function, Sinha et al [106] looked for the Crygs gene in the mouse eye and found the γS mRNA to be present in the retina as well as the cornea, though not in the iris.…”

Section: Section Iii: Gamma Crystallins Outside the Lensmentioning

confidence: 99%

“…Since then, several papers have appeared which have tried to follow up on this idea [107,108]. However, all of these studies, while mentioning βγ-crystallins, focus on the roles of specific β-crystallins such as βA3/ A1 [108], or βB2 [105], and these too on rodent eyes, rather than humans. And when talking about γ-crystallins, reference is made invariably to the mixture rather than a single member such as γS, γD or γC.…”

Section: Section Iii: Gamma Crystallins Outside the Lensmentioning

confidence: 99%

See 1 more Smart Citation

Gamma crystallins of the human eye lens

Vendra

Khan

Chandani

et al. 2016

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

Section: Section Iii: Gamma Crystallins Outside the Lensmentioning

confidence: 99%

Section: Section Iii: Gamma Crystallins Outside the Lensmentioning

confidence: 99%

Gamma crystallins of the human eye lens

Vendra

Khan

Chandani

et al. 2016

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

“…Indeed, βB2-crystallin is secreted by cultured retinas during axonal regeneration and aids elongation in vitro when added to culture medium (Liedtke et al, 2007). Furthermore, intravitreal injections of purified β-crystallins induced a regenerative state in retinal ganglion cells after axotomy or optic nerve crush in rats, demonstrating strong evidence for a therapeutic use for β-crystallins (Fischer et al, 2008; Thanos et al, 2014). However, before β-crystallins can be used as therapy for human eye diseases or injuries, the underlying mechanisms need to be more properly investigated.…”

mentioning

confidence: 92%

BetaB2-crystallin mutations associated with cataract and glaucoma leads to mitochondrial alterations in lens epithelial cells and retinal neurons

Dulle

Rübsam

Garnai

et al. 2017

Experimental Eye Research

View full text Add to dashboard Cite

Crystallin proteins are the most prominent protein of the lens and have been increasingly shown to play critical roles in other tissues, especially the retina. Members of all 3 sub-families of crystallins, alpha-, beta- and gamma-crystallins have been reported in the retina during diabetes, traumatic injury and other retinal diseases. While their specific role in the retina is still unclear and may vary, beta-crystallin proteins have been shown to play a critical role in ganglion cell survival following trauma. We recently reported the correlation between a gene conversion in the betaB2-crystallin gene and a phenotype of familial congenital cataract. Interestingly, in half of the patients, this phenotype was associated with glaucoma. Taken together, these data suggested that the mutations we recently reported could have an impact on the role of betaB2-crystallin in both lens epithelial cells and retinal neurons. Consistent with this hypothesis, we show in the current study that the gene conversion leading to an amino acid conversion lead to a loss of solubility and a change of subcellular localization of betaB2-crystallin in both cell types. While the overall observations were similar in both cell types, there were some important nuances between them, suggesting different roles and regulation of betaB2-crystallin in lens cells versus retinal neurons. The data reported in this study strongly support a significant role of betaB2-crystallin in both lenticular and retinal ocular tissues and warrant further analysis of its regulation and its impact not only in cataract formation but also in retinal neurodegenerative diseases.

show abstract

“…αB-crystallin/HspB5 is a widely expressed sHsp first identified in the lens that has been implicated in the pathogenesis of diverse diseases, including myopathies, neurodegenerative disorders, cataracts and cancer (Boelens, 2014). Although there have been several recent reviews highlighting new structural insights and its role in other diseases (Hochberg & Benesch, 2014; Thanos et al, 2014; van der Smagt et al, 2014; Bakthisaran et al, 2015; Haslbeck & Vierling, 2015; Haslbeck et al, 2015; Nagaraj et al, 2015; Treweek et al, 2015), the present review will focus on the mechanisms by which αB-crystallin inhibits cancer cell death, its emerging role as a pathogenic driver in metastasis, and therapeutic efforts to target αB-crystallin in cancer. Insights regarding the role of other sHsps, including Hsp27, in cancer have been reviewed elsewhere (Arrigo et al, 2007; Acunzo et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

αB-crystallin: Portrait of a malignant chaperone as a cancer therapeutic target

Malin

Petrovič

Strekalova

et al. 2016

Pharmacology & Therapeutics

View full text Add to dashboard Cite

αB-crystallin is a widely expressed member of the small heat shock protein family that protects cells from stress by its dual function as a molecular chaperone to preserve proteostasis and as a cell death antagonist that negatively regulates components of the conserved apoptotic cell death machinery. Deregulated expression of αB-crystallin occurs in a broad array of solid tumors and has been linked to tumor progression and poor clinical outcomes. This review will focus on new insights into the molecular mechanisms by which oncogenes, oxidative stress, matrix detachment and other tumor microenvironmental stressors deregulate αB-crystallin expression. We will also review accumulating evidence pointing to an essential role for αB-crystallin in the multi-step metastatic cascade whereby tumor cells colonize distant organs by circumventing a multitude of barriers to cell migration and survival. Finally, we will evaluate emerging strategies to therapeutically target αB-crystallin and/or interacting proteins to selectively activate apoptosis and/or derail the metastatic cascade in an effort to improve outcomes for patients with metastatic disease.

show abstract

Role of crystallins in ocular neuroprotection and axonal regeneration

Cited by 62 publications

References 147 publications

Gamma crystallins of the human eye lens

Gamma crystallins of the human eye lens

BetaB2-crystallin mutations associated with cataract and glaucoma leads to mitochondrial alterations in lens epithelial cells and retinal neurons

αB-crystallin: Portrait of a malignant chaperone as a cancer therapeutic target

Contact Info

Product

Resources

About