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Table 1 Pharmacological targeting of molecular chaperones in models of synucleinopathies

From: Molecular chaperones and protein folding as therapeutic targets in Parkinson’s disease and other synucleinopathies

A) HSP90 inhibitors

Compound

Disease model

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Reference

Geldanamycin

Drosophila melanogaster

• Hsp70 levels

Auluck et al. 2002 [167]

• Toxicity

 

Cell model

• α-synuclein aggregation

McLean et al. 2004 [168]

• α-synuclein and chaperone levels

• Toxicity

 

Drosophila melanogaster

• α-synuclein aggregation

Auluck 2005 et al. [169]

• Hsp70 levels

• Toxicity

 

Saccharomyces cerevisiae

• Oxidative stress

Flower et al. 2005 [170]

• Cytochrome c release

 

Cell model

• Intracellular and extracellular α-synuclein levels

Liu et al. 2009 [171]

• Neurite length

• Toxicity

 

Cell model

• α-synuclein aggregation

Emmanouilidou et al. 2010 [172]

• Proteasome activity

• Levels of poly-ubiquitinated proteins

17-AAG

Cell model

• Extracellular α-synuclein oligomers

Danzer et al. 2011 [46]

• Extracellular α-synuclein and Hsp70 levels

 

Cell model

• α-synuclein oligomers

Putcha et al. 2010 [45]

• α-synuclein and Hsp70 levels

• Toxicity

 

Cell model

• α-synuclein aggregation

Riedel et al. 2010 [173]

• Chaperone levels

• Macroautophagy markers

• Toxicity

SNX compounds

Cell model

• α-synuclein oligomers

Putcha et al. 2010 [45]

• α-synuclein and Hsp70 levels

• Toxicity

B) Enhancers of HSF-1

Compound

Disease model

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Reference

Carbenoxolone

Cell model

• α-synuclein aggregation

Kilpatrick et al. 2013 [174]

• α-synuclein and chaperone levels

• HSF-1 localization

C) Chemical chaperones

Compound

Disease model

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Reference

Trehalose

Cell model

• α-synuclein levels

Sarkar et al. 2007 [175]

• Macroautophagy markers

 

In vitro assays

• α-synuclein aggregation

Yu et al. 2012 [176]

Mannitol

In vitro assays,

Drosophila melanogaster,

α-synuclein transgenic mice

• α-synuclein aggregation

Shaltiel-Karyo et al. 2013 [177]

• α-synuclein and Hsp70 levels

• Behavioral deficits

• Toxicity

Mannosylglycerate

Saccharomyces cerevisiae

• α-synuclein aggregation

Faria et al. 2013 [178]

• α-synuclein and chaperone levels

• Toxicity

4-phenylbutyrate

α-synuclein transgenic mice

• Phosphorylated α-synuclein

Ono et al. 2009 [179]

• Dopamine levels

• Behavioral deficits

• Toxicity