Hsp60 Protects against Amyloid β Oligomer Synaptic Toxicity via Modification of Toxic Oligomer Conformation

Claudia Marino, Balaji Krishnan, Francesco Cappello, Giulio Taglialatela

Research output: Contribution to journalArticle

Abstract

Alzheimer's disease (AD) is the leading cause of dementia worldwide. While the etiology of AD remains uncertain, neurotoxic effects of amyloid beta oligomers (Aβo) on synaptic function, a well-established early event in AD, is an attractive area for the development of novel strategies to modify or cease the disease's progression. In this work, we tested the protective action of the mitochondrial chaperone Hsp60 against Aβo neurotoxicity, by determining the direct effect of Hsp60 in changing Aβo toxic conformations and thus reducing their dysfunctional synaptic binding and consequent suppression of long-term potentiation. Our data suggest that Hsp60 has a direct impact on Aβo, resulting in a reduction of cytotoxicity and rescue of Aβo-driven synaptic damage, thus proposing Hsp60 as an attractive therapeutic target candidate.

Original languageEnglish (US)
JournalACS Chemical Neuroscience
DOIs
StatePublished - Jan 1 2019

Fingerprint

Poisons
Oligomers
Amyloid
Toxicity
Conformations
Alzheimer Disease
Long-Term Potentiation
Cytotoxicity
Dementia
Disease Progression

Keywords

  • Alzheimer's disease
  • Amyloid-β oligomers
  • chaperonin
  • Hsp60
  • synaptic plasticity
  • synaptic toxicity

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

Cite this

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abstract = "Alzheimer's disease (AD) is the leading cause of dementia worldwide. While the etiology of AD remains uncertain, neurotoxic effects of amyloid beta oligomers (Aβo) on synaptic function, a well-established early event in AD, is an attractive area for the development of novel strategies to modify or cease the disease's progression. In this work, we tested the protective action of the mitochondrial chaperone Hsp60 against Aβo neurotoxicity, by determining the direct effect of Hsp60 in changing Aβo toxic conformations and thus reducing their dysfunctional synaptic binding and consequent suppression of long-term potentiation. Our data suggest that Hsp60 has a direct impact on Aβo, resulting in a reduction of cytotoxicity and rescue of Aβo-driven synaptic damage, thus proposing Hsp60 as an attractive therapeutic target candidate.",
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AU - Krishnan, Balaji

AU - Cappello, Francesco

AU - Taglialatela, Giulio

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AB - Alzheimer's disease (AD) is the leading cause of dementia worldwide. While the etiology of AD remains uncertain, neurotoxic effects of amyloid beta oligomers (Aβo) on synaptic function, a well-established early event in AD, is an attractive area for the development of novel strategies to modify or cease the disease's progression. In this work, we tested the protective action of the mitochondrial chaperone Hsp60 against Aβo neurotoxicity, by determining the direct effect of Hsp60 in changing Aβo toxic conformations and thus reducing their dysfunctional synaptic binding and consequent suppression of long-term potentiation. Our data suggest that Hsp60 has a direct impact on Aβo, resulting in a reduction of cytotoxicity and rescue of Aβo-driven synaptic damage, thus proposing Hsp60 as an attractive therapeutic target candidate.

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