Expression of heat shock proteins in Alzheimer's disease

Hamos, James E.; Oblas, B.; Pulaski-Salo, D.; Wj, Welch; Bole, David G.; Drachman, David A.

doi:10.1212/wnl.41.3.345

Cited by 243 publications

(116 citation statements)

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“…Therefore, the increase of BiP in apoptotic SH-SY5Y cells might represent a neuroprotective mechanism, aimed at counteracting AEA-induced cell death. For instance, BiP is up-regulated in neurons of Alzheimer disease brains, where this protein has indeed been shown to play a neuroprotective role (53,54). Consistently, we observed that overexpression of BiP confers resistance to AEA-induced apoptosis in human neuronal cells.…”

Section: Discussionsupporting

confidence: 84%

Characterization of the Endocannabinoid System in Human Neuronal Cells and Proteomic Analysis of Anandamide-induced Apoptosis

Pasquariello

Catanzaro

Marzano

et al. 2009

Journal of Biological Chemistry

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Anandamide (AEA) is an endogenous agonist of type 1 cannabinoid receptors (CB1R) that, along with metabolic enzymes of AEA and congeners, compose the "endocannabinoid system." Here we report the biochemical, morphological, and functional characterization of the endocannabinoid system in human neuroblastoma SH-SY5Y cells that are an experimental model for neuronal cell damage and death, as well as for major human neurodegenerative disorders. We also show that AEA dose-dependently induced apoptosis of SH-SY5Y cells. Through proteomic analysis, we further demonstrate that AEA-induced apoptosis was paralleled by an ϳ3 to ϳ5-fold up-regulation or down-regulation of five genes; IgG heavy chain-binding protein, stress-induced phosphoprotein-1, and triose-phosphate isomerase-1, which were up-regulated, are known to act as antiapoptotic agents; actin-related protein 2/3 complex subunit 5 and peptidylprolyl isomerase-like protein 3 isoform PPIL3b were down-regulated, and the first is required for actin network formation whereas the second is still function-orphan. Interestingly, only the effect of AEA on BiP was reversed by the CB1R antagonist SR141716, in SH-SY5Y cells as well as in human neuroblastoma LAN-5 cells (that express a functional CB1R) but not in SK-NBE cells (which do not express CB1R). Silencing or overexpression of BiP increased or reduced, respectively, AEA-induced apoptosis of SH-SY5Y cells. In addition, the expression of BiP and of the BiP-related apoptotic markers p53 and PUMA was increased by AEA through a CB1R-dependent pathway that engages p38 and p42/44 mitogen-activated protein kinases. Consistently, this effect of AEA was minimized by SR141716. In conclusion, we identified BiP as a key protein in neuronal apoptosis induced by AEA.Endocannabinoids bind to and activate both type 1 (CB1R) 4 and type 2 (CB2R) cannabinoid receptors and are widely recognized as important regulators of central and peripheral functions (1-3). The most studied endocannabinoids are anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) (1, 3). AEA, unlike 2-AG, binds to and activates also transient receptor potential vanilloid 1 (TRPV1), thus being considered a true "endovanilloid" (4).The "endocannabinoid system (ECS)" includes the receptors, their ligands AEA and 2-AG, and the enzymes that synthesize (N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD) and diacylglycerol lipase (DAGL)) or degrade (fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL)) AEA and 2-AG, respectively (1-3). On the other hand, there is still controversy about the identity and even the existence of purported "endocannabinoid transporters" that have not yet been cloned, isolated, or characterized (5). A growing interest is concerned with the ability of AEA to induce apoptosis in neuronal and non-neuronal cells (for comprehensive reviews see Refs. 6 -9). Such a pro-apoptotic activity of AEA

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Section: Discussionsupporting

confidence: 84%

Characterization of the Endocannabinoid System in Human Neuronal Cells and Proteomic Analysis of Anandamide-induced Apoptosis

Pasquariello

Catanzaro

Marzano

et al. 2009

Journal of Biological Chemistry

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“…Early studies using immunohistochemistry and immunoblotting suggested that expression of both HSP70-class (34,35) and ␣B-crystallin-related proteins (36,37) was increased in AD brains, and both classes of proteins were associated with senile plaques. A more recent study using two-dimensional PAGE coupled with mass spectrometry confirmed the increased expression of ␣B-crystallin but found that specific HSP70-class proteins may be increased (HSPA4), decreased (HSPA8), or unchanged (HSPA1B, HSPA5) in specific regions of AD brains (38).…”

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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“…All samples contained 90% H 2 O and 10% (v/v) D 2 O. 15 N, 1 H HSQC experiments were performed with 1024 points ϫ 128 increments and referenced according to the water resonance frequency. NMR data were processed using NMRPipe (48) and analyzed using SPARKY (T. D. Goddard and D. G. Kneller, SPARKY 3, University of California, San Francisco).…”

Section: Methodsmentioning

confidence: 99%

“…Molecular chaperones have evolved to counteract misfolding in the cell. Examples are the heat-shock proteins (Hsp) 70, Hsp90, and Hsp104 (13)(14)(15)(16) and * This work was supported by the Swedish Research Council.…”

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confidence: 99%

BRICHOS Domains Efficiently Delay Fibrillation of Amyloid β-Peptide

Willander

Presto

Askarieh

et al. 2012

Journal of Biological Chemistry

135

160

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Background: Alzheimer disease (AD) is associated with A␤ protein misfolding and aggregation into fibrils rich in ␤-sheet structure. Results: BRICHOS domains prevent fibril formation of A␤ far below the stoichiometric ratio. Conclusion: A␤ is maintained as an unstructured monomer in the presence of BRICHOS. Significance: BRICHOS domain can have a natural protective role against A␤ aggregation, which may open new routes toward AD therapy.

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Expression of heat shock proteins in Alzheimer's disease

Cited by 243 publications

References 0 publications

Characterization of the Endocannabinoid System in Human Neuronal Cells and Proteomic Analysis of Anandamide-induced Apoptosis

Characterization of the Endocannabinoid System in Human Neuronal Cells and Proteomic Analysis of Anandamide-induced Apoptosis

Interaction of intracellular β amyloid peptide with chaperone proteins

BRICHOS Domains Efficiently Delay Fibrillation of Amyloid β-Peptide

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