Skip to main content

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 Readout 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 Readout 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 Readout 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