To understand the mechanism of VP1-001, we tested the ability of its enantiomer, ent-VP1-001, to bind and stabilize αB-crystallin (cryAB) in vitro and to produce a similar therapeutic effect in cryAB(R120G) mutant and aged wild-type mice with cataracts.
In this study, we screened for polymorphisms in crystallin alpha A (CRYAA) and alpha B (CRYAB) genes in 200 patients over 40 years of age, diagnosed with age-related cataract (ARC; nuclear and cortical cataracts).
Dominant mutations in the alpha-B crystallin (CryAB) gene are responsible for a number of inherited human disorders, including cardiomyopathy, skeletal muscle myopathy, and cataracts.
To describe later retinal degeneration following childhood cataract surgery without intraocular lens implantation in a consanguineous family with developmental cataract from homozygous p.R56W mutation in CRYAB, a gene that encodes a heat-shock protein (alphaB-crystallin) in both retina and the lens.
Non-syndromic, hereditary human cataract development is linked to point mutations in the CRYAA and CRYAB genes which encode alphaA and alphaB-crystallin.
These knock-in αB-R120G mice are a valuable model of the developmental and molecular biological mechanisms that underlie the pathophysiology of human hereditary cataracts and myopathy.
Structural and functional characterization of D109H and R69C mutant versions of human αB-crystallin: the biochemical pathomechanism underlying cataract and myopathy development.
Mutations of HSPB5 (also known as CRYAB or αB-crystallin), a bona fide heat shock protein and molecular chaperone encoded by the HSPB5 (crystallin, alpha B) gene, are linked to multisystem disorders featuring variable combinations of cataracts, cardiomyopathy, and skeletal myopathy.
Physico-chemical properties of G154S, R157H and A171T mutants of αB-crystallin (HspB5) associated with congenital human diseases including certain myopathies and cataract were investigated.
Since the CPF is unique to nuclear cataract lenses, these data suggest that alpha-crystallin, and alpha B-crystallin in particular, may be implicated in the cataract process.
In the context of the αB-crystallin structure and the finding that it forms heterogeneous multimers, our structural studies suggest a potential mechanism for cataract formation via the depletion of the finite αB-crystallin population of the lens.
Surgical removal of cataracts is typically incomplete, and we estimate that this disease is associated with alpha-B crystallin (CRYAB) secreted from the retained lens material.
Despite their importance in maintaining cellular health, modifications and mutations to αA and αB appear to play a role in disease states such as cataract and myopathies.
Genetic mutations in the human small heat shock protein αB-crystallin have been implicated in autosomal cataracts and skeletal myopathies, including heart muscle diseases (cardiomyopathy).