αB-Crystallin is present in reactive glia in Creutzfeldt-Jakob disease

Renkawek, K; Jong, Wilfried W. de; Merck, Karin B.; Frenken, C. W. G. M.; Workum, F. P. A. van; Bosman, G.J.C.G.M.

doi:10.1007/bf00296796

Cited by 155 publications

(75 citation statements)

References 16 publications

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“…For example, induction of sHsps has been reported in Alexander's disease [60], Creutzfeldt-Jakob disease [61], Alzheimer's disease, [62,63] and other neurological conditions [64][65][66][67][68][69]. Moreover, sHsps have been found to co-localize with the protein aggregates associated with a number of these protein misfolding diseases and/or are found at significant levels in neurons that surround the deposits (see below for details).…”

Section: Shsps and Diseasementioning

confidence: 99%

“…Significantly, in mice lacking αB-crystallin, the onset and severity of aggregation was markedly accelerated [92]. sHsps have also been found to be highly expressed in astrocytes in the brains of patients with Creutzfeldt-Jakob disease (in which the fibril forming protein is the prion protein) [61] and the expression of Hsp25 and αB-crystallin is increased in transgenic mouse models of familial amyotrophic lateral sclerosis [83].…”

Section: Shsps and Alzheimer's Diseasementioning

confidence: 99%

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Crystallin proteins and amyloid fibrils

Ecroyd

Carver

2008

Cell. Mol. Life Sci.

221

234

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Improper protein folding (misfolding) can lead to the formation of disordered (amorphous) or ordered (amyloid fibril) aggregates. The major lens protein, alpha-crystallin, is a member of the small heat-shock protein (sHsp) family of intracellular molecular chaperone proteins that prevent protein aggregation. Whilst the chaperone activity of sHsps against amorphously aggregating proteins has been well studied, its action against fibril-forming proteins has received less attention despite the presence of sHsps in deposits found in fibril-associated diseases (e.g. Alzheimer's and Parkinson's). In this review, the literature on the interaction of alpha B-crystallin and other sHsps with fibril-forming proteins is summarized. In particular, the ability of sHsps to prevent fibril formation, their mechanisms of action and the possible in vivo consequences of such associations are discussed. Finally, the fibril-forming propensity of the crystallin proteins and its implications for cataract formation are described along with the potential use of fibrillar crystallin proteins as bionanomaterials. Improper protein folding (misfolding) can lead to the formation of disordered (amorphous) or ordered (amyloid fibril) aggregates. The major lens protein, α-crystallin, is a member of the small heat-shock protein (sHsp) family of intracellular molecular chaperone proteins that prevent protein aggregation. Whilst the chaperone activity of sHsps against amorphously aggregating proteins has been well studied, its action against fibril-forming proteins has received less attention despite the presence of sHsps in deposits found in fibril-associated diseases (e.g. Alzheimer's and Parkinson's). In this review, the literature on the interaction of αB-crystallin and other sHsps with fibril-forming proteins is summarized. In particular, the ability of sHsps to prevent fibril formation, their mechanisms of action and the possible in vivo consequences of such associations are discussed. Finally, the fibril-forming propensity of the crystallin proteins and its implications for cataract formation are described along with the potential use of fibrillar crystallin proteins as bionanomaterials.

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Section: Shsps and Diseasementioning

confidence: 99%

Section: Shsps and Alzheimer's Diseasementioning

confidence: 99%

Crystallin proteins and amyloid fibrils

Ecroyd

Carver

2008

Cell. Mol. Life Sci.

221

234

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“…The importance of ␣-crystallins as molecular chaperones was demonstrated by knock-out mice, in which the deletion of ␣A-crystallin led to young onset cataract formation (15). The functional importance of ␣B-crystallin is not restricted to the eye lens, because it was shown to be associated with a number of neuropathological protein folding diseases, including Alzheimer's, Parkinson's, and Creutzfeldt-Jakob disease (16,17). Additionally, ␣B-crystallin is the most abundant gene transcript present in early active multiple sclerosis lesions (18), and it appears to exhibit anti-apoptotic as well as neuroprotective functions (19,20).…”

mentioning

confidence: 99%

The eye lens chaperone α-crystallin forms defined globular assemblies

Peschek

Braun

Franzmann

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

131

121

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␣-Crystallins are molecular chaperones that protect vertebrate eye lens proteins from detrimental protein aggregation. ␣B-Crystallin, 1 of the 2 ␣-crystallin isoforms, is also associated with myopathies and neuropathological diseases. Despite the importance of ␣-crystallins in protein homeostasis, only little is known about their quaternary structures because of their seemingly polydisperse nature. Here, we analyzed the structures of recombinant ␣-crystallins using biophysical methods. In contrast to previous reports, we show that ␣B-crystallin assembles into defined oligomers consisting of 24 subunits. The 3-dimensional (3D) reconstruction of ␣B-crystallin by electron microscopy reveals a spherelike structure with large openings to the interior of the protein.␣A-Crystallin forms, in addition to complexes of 24 subunits, also smaller oligomers and large clusters consisting of individual oligomers. This propensity might explain the previously reported polydisperse nature of ␣-crystallin.electron microscopy ͉ molecular chaperone ͉ protein aggregation ͉ small heat shock protein ͉ stress response

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“…It is possible that, in the lens, ␣-crystallin may chaperone the formation of the transparent and appropriately refracting ensemble and may also keep it that way by interacting with damaged proteins. ␣-Crystallin may have a similar function of interacting with aged or damaged proteins in Creutzfeldt-Jakob disease brain (12) and ischemic heart tissue (13). ␣B-crystallin may even play a regulatory role in cytomorphological rearrangements during development (14).…”

mentioning

confidence: 99%

Differential Temperature-dependent Chaperone-like Activity of αA- and αB-crystallin Homoaggregates

Datta

Rao

1999

Journal of Biological Chemistry

104

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␣-Crystallin, a heteromultimeric protein made up of ␣A-and ␣B-crystallins, functions as a molecular chaperone in preventing the aggregation of proteins. We have shown earlier that structural perturbation of ␣-crystallin can enhance its chaperone-like activity severalfold. The two subunits of ␣-crystallin have extensive sequence homology and individually display chaperonelike activity. We have investigated the chaperone-like activity of ␣A-and ␣B-crystallin homoaggregates against thermal and nonthermal modes of aggregation. We find that, against a nonthermal mode of aggregation, ␣B-crystallin shows significant protective ability even at subphysiological temperatures, at which ␣A-crystallin or heteromultimeric ␣-crystallin exhibit very little chaperone-like activity. Interestingly, differences in the protective ability of these homoaggregates against the thermal aggregation of ␤ L -crystallin is negligible. To investigate this differential behavior, we have monitored the temperature-dependent structural changes in both the proteins using fluorescence and circular dichroism spectroscopy. Intrinsic tryptophan fluorescence quenching by acrylamide shows that the tryptophans in ␣B-crystallin are more accessible than the lone tryptophan in ␣A-crystallin even at 25°C. Protein-bound 8-anilinonaphthalene-1-sulfonate fluorescence demonstrates the higher solvent accessibility of hydrophobic surfaces on ␣B-crystallin. Circular dichroism studies show some tertiary structural changes in ␣A-crystallin above 50°C. ␣B-crystallin, on the other hand, shows significant alteration of tertiary structure by 45°C. Our study demonstrates that despite a high degree of sequence homology and their generally accepted structural similarity, ␣B-crystallin is much more sensitive to temperaturedependent structural perturbation than ␣A-or ␣-crystallin and shows differences in its chaperone-like properties. These differences appear to be relevant to temperature-dependent enhancement of chaperone-like activity of ␣-crystallin and indicate different roles for the two proteins both in ␣-crystallin heteroaggregate and as separate proteins under stress conditions. ␣-Crystallin is a major protein of the mammalian lens and constitutes as much as 50% of its dry weight. Studies over the past few years have shown that ␣-crystallin is expressed in several nonlenticular tissues such as heart, brain, and kidney, and its expression is enhanced severalfold during stress and disease conditions (1-6). ␣-Crystallin is shown to have homology with small heat shock proteins (7-10). Horwitz (11) shows that ␣-crystallin can prevent the thermal aggregation of ␤-and ␥-crystallins and a few other proteins like a molecular chaperone. Demonstration of chaperone-like activity of ␣-crystallin has provided an excellent opportunity to investigate the mechanistic aspects of chaperone function in general and the role of ␣-crystallin under stress conditions in particular. It is possible that, in the lens, ␣-crystallin may chaperone the formation of the transparent and appropriately ...

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αB-Crystallin is present in reactive glia in Creutzfeldt-Jakob disease

Cited by 155 publications

References 16 publications

Crystallin proteins and amyloid fibrils

Crystallin proteins and amyloid fibrils

The eye lens chaperone α-crystallin forms defined globular assemblies

Differential Temperature-dependent Chaperone-like Activity of αA- and αB-crystallin Homoaggregates

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