secHsp70 as a tool to approach amyloid-β42 and other extracellular amyloids

Lorena De Mena, Deepak Chhangani, Pedro Fernandez-Funez, Diego E. Rincon-Limas

Research output: Contribution to journalComment/debate

6 Citations (Scopus)

Abstract

Self-association of amyloidogenic proteins is the main pathological trigger in a wide variety of neurodegenerative disorders. These aggregates are deposited inside or outside the cell due to hereditary mutations, environmental exposures or even normal aging. Cumulative evidence indicates that the heat shock chaperone Hsp70 possesses robust neuroprotection against various intracellular amyloids in Drosophila and mouse models. However, its protective role against extracellular amyloids was largely unknown as its presence outside the cells is very limited. Our recent manuscript in PNAS revealed that an engineered form of secreted Hsp70 (secHsp70) is highly protective against toxicity induced by extracellular deposition of the amyloid-β42 (Aβ42) peptide. In this Extra View article, we extend our analysis to other members of the heat shock protein family. We created PhiC31-based transgenic lines for human Hsp27, Hsp40, Hsp60 and Hsp70 and compared their activities in parallel against extracellular Aβ42. Strikingly, only secreted Hsp70 exhibits robust protection against Aβ42-triggered toxicity in the extracellular milieu. These observations indicate that the ability of secHsp70 to suppress Aβ42 insults is quite unique and suggest that targeted secretion of Hsp70 may represent a new therapeutic approach against Aβ42 and other extracellular amyloids. The potential applications of this engineered chaperone are discussed.

Original languageEnglish (US)
Pages (from-to)179-184
Number of pages6
JournalFly
Volume11
Issue number3
DOIs
StatePublished - Jul 3 2017

Fingerprint

amyloid
toxicity
neurodegenerative diseases
protein aggregates
heat shock proteins
heat stress
Drosophila
animal models
secretion
genetically modified organisms
peptides
cells
mutation
therapeutics

Keywords

  • Alzheimer disease
  • Amyloid β
  • Drosophila
  • Hsp27
  • Hsp40
  • Hsp60
  • Hsp70
  • ataxin 3
  • neurodegeneration
  • protein misfolding

Cite this

secHsp70 as a tool to approach amyloid-β42 and other extracellular amyloids. / De Mena, Lorena; Chhangani, Deepak; Fernandez-Funez, Pedro; Rincon-Limas, Diego E.

In: Fly, Vol. 11, No. 3, 03.07.2017, p. 179-184.

Research output: Contribution to journalComment/debate

De Mena, Lorena ; Chhangani, Deepak ; Fernandez-Funez, Pedro ; Rincon-Limas, Diego E. / secHsp70 as a tool to approach amyloid-β42 and other extracellular amyloids. In: Fly. 2017 ; Vol. 11, No. 3. pp. 179-184.
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