Small heat shock proteins inhibit in vitro Aβ<sub>1–42</sub> amyloidogenesis

Kudva, Yogish C.; Hiddinga, Henry J.; Butler, Peter C.; Mueske, Cheryl S.; Eberhardt, Norman L.

doi:10.1016/s0014-5793(97)01180-0

Cited by 104 publications

(68 citation statements)

References 39 publications

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“…In vitro, ␣B-crystallin can physically interact with A␤1-40 (39) and has been reported to inhibit fibril formation by A␤1-42 (40). However, A␤1-40 preparations preincubated with ␣B-crystallin have been reported to have enhanced toxicity, despite reduced fibril formation (41).…”

Section: Discussionmentioning

confidence: 99%

Interaction of intracellular β amyloid peptide with chaperone proteins

Fonte

Kapulkin²,

Taft³

et al. 2002

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

199

151

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Expression of the human β amyloid peptide (Aβ) in transgenic Caenorhabditis elegans animals can lead to the formation of intracellular immunoreactive deposits as well as the formation of intracellular amyloid. We have used this model to identify proteins that interact with intracellular Aβ in vivo . Mass spectrometry analysis of proteins that specifically coimmunoprecipitate with Aβ has identified six likely chaperone proteins: two members of the HSP70 family, three αB-crystallin-related small heat shock proteins (HSP-16s), and a putative ortholog of a mammalian small glutamine-rich tetratricopeptide repeat-containing protein proposed to regulate HSP70 function. Quantitative reverse transcription–PCR analysis shows that the small heat shock proteins are also transcriptionally induced by Aβ expression. Immunohistochemistry demonstrates that HSP-16 protein closely colocalizes with intracellular Aβ in this model. Transgenic animals expressing a nonaggregating Aβ variant, a single-chain Aβ dimer, show an altered pattern of coimmunoprecipitating proteins and an altered cellular distribution of HSP-16. Double-stranded RNA inhibition of R05F9.10, the putative C. elegans ortholog of the human small glutamine-rich tetratricopeptide-repeat-containing protein (SGT), results in suppression of toxicity associated with Aβ expression. These results suggest that chaperone function can play a role in modulating intracellular Aβ metabolism and toxicity.

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Section: Discussionmentioning

confidence: 99%

Interaction of intracellular β amyloid peptide with chaperone proteins

Fonte

Kapulkin²,

Taft³

et al. 2002

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

199

151

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“…In contrast to these studies, Kudva et al [100] reported that α-crystallin (made up of both αA-and αB-crystallin subunits) had no effect on the initial rate of fibril formation by Aβ(1-42) when used at a 1.0: 0.3 molar ratio of Aβ(1-42): α-crystallin. Wilhemus et al [101] showed that αB-crystallin (at a 1.0: 1.0 molar ratio) completely inhibited the formation of fibrils by DAβ(1-40) (a Dutch mutation of Aβ(1-40) where Glu22 is replaced by Gln which forms fibrils more rapidly than the wild-type Aβ(1-40) peptide) and delayed the formation of fibrils by Aβ(1-42) (as assessed by TEM).…”

Section: Shsps and The Aβ Peptidesmentioning

confidence: 86%

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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“…The by no means complete list includes eye lens transparency (33); thermotolerance (169,171,177,198,248,261,270,332,362); resistance to apoptosis (10,35,45,(199)(200)(201); cytoskeleton modulation (20,104,172,184,207,232); prevention of amyloid formation (165,307); human diseases (48); various developmental processes in animals (11,118,181,185,203), plants (349), and bacteria (115); protection against oxidative stress (109,259); desiccation tolerance (354); protection of the photosynthetic apparatus (113,221) or of mitochondrial NADH:ubiquinone oxidoreductase (complex I) (68,69); microbial pathogenicity (2,54,228,283,342,363,365); symbiotic and pathogenic plantmicrobe interactions (16,…”

Section: Other Functions Of ␣-Heat Shock Proteinsmentioning

confidence: 99%

α-Crystallin-Type Heat Shock Proteins: Socializing Minichaperones in the Context of a Multichaperone Network

Narberhaus

2002

Microbiol Mol Biol Rev

503

415

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SUMMARY α-Crystallins were originally recognized as proteins contributing to the transparency of the mammalian eye lens. Subsequently, they have been found in many, but not all, members of the Archaea, Bacteria, and Eucarya. Most members of the diverse α-crystallin family have four common structural and functional features: (i) a small monomeric molecular mass between 12 and 43 kDa; (ii) the formation of large oligomeric complexes; (iii) the presence of a moderately conserved central region, the so-called α-crystallin domain; and (iv) molecular chaperone activity. Since α-crystallins are induced by a temperature upshift in many organisms, they are often referred to as small heat shock proteins (sHsps) or, more accurately, α-Hsps. α-Crystallins are integrated into a highly flexible and synergistic multichaperone network evolved to secure protein quality control in the cell. Their chaperone activity is limited to the binding of unfolding intermediates in order to protect them from irreversible aggregation. Productive release and refolding of captured proteins into the native state requires close cooperation with other cellular chaperones. In addition, α-Hsps seem to play an important role in membrane stabilization. The review compiles information on the abundance, sequence conservation, regulation, structure, and function of α-Hsps with an emphasis on the microbial members of this chaperone family.

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Small heat shock proteins inhibit in vitro Aβ_1–42 amyloidogenesis

Cited by 104 publications

References 39 publications

Interaction of intracellular β amyloid peptide with chaperone proteins

Interaction of intracellular β amyloid peptide with chaperone proteins

Crystallin proteins and amyloid fibrils

α-Crystallin-Type Heat Shock Proteins: Socializing Minichaperones in the Context of a Multichaperone Network

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Small heat shock proteins inhibit in vitro Aβ1–42 amyloidogenesis

Cited by 104 publications

References 39 publications

Interaction of intracellular β amyloid peptide with chaperone proteins

Interaction of intracellular β amyloid peptide with chaperone proteins

Crystallin proteins and amyloid fibrils

α-Crystallin-Type Heat Shock Proteins: Socializing Minichaperones in the Context of a Multichaperone Network

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Small heat shock proteins inhibit in vitro Aβ_1–42 amyloidogenesis