The role of heat shock proteins in Amyotrophic Lateral Sclerosis: The therapeutic potential of Arimoclomol

Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice

“…32,33 In addition, as a unique tumor treatment, 17-AAG can effectively inhibit many cell signal transduction pathways that maintain the proliferation and survival of tumor cells. 34 Hence, we propose a brand-new combined therapy that targets cancer stem cells. In this therapy, physical targeting is combined with biological targeting using an anti-CD90 monoclonal antibody to ensure specificity.…”

Induction of heat shock proteins in differentiated human neuronal cells following co-application of celastrol and arimoclomol

“…In a mouse model of ALS, arimoclomol was found to improve motor performance and extend lifespan of SOD1 G93A transgenic mice (Kieran et al 2004;Kalmar et al 2008Kalmar et al , 2014McGoldrick et al 2013;Poppe et al 2014). Interestingly, arimoclomol is now in phase IIb/III clinical trials (ClinicalTrials.gov identifier: NCT00706147) for the treatment of ALS (Genc and Ozdinler 2013).…”

“…Celastrol has shown therapeutic potential in a number of animal models of neurodegenerative diseases including ALS (Kiaei et al 2005), Parkinson's disease (Cleren et al 2005), polyglutamine disease (Zhang and Sarge 2007), and Alzheimer's disease (Paris et al 2010) and has the added benefit of being a potent anti-inflammatory and anti-oxidant (Allison et al 2001;Jung et al 2007;Faust et al 2009;Kim et al 2009;Venkatesha et al 2012;Wong et al 2012;Yang et al 2014;Sharma et al 2015). Arimoclomol is a co-inducer that amplifies the induction of Hsps, prolongs life and motor performance in an animal model of ALS (Hargitai et al 2003;Kieran et al 2004;Kalmar et al 2008Kalmar et al , 2014, and is currently in clinical trials on human patients (ClinicalTrials.gov identifier: NCT00706147). Coapplication of celastrol and arimoclomol represents a potential multitarget therapeutic strategy for the treatment of neurodegenerative diseases that could impact disease mechanisms, such as synaptic dysfunction, at early stages of disease progression.…”

“…Another compound that modulates the heat shock response is arimoclomol, which has been shown to improve motor performance and extend lifespan in SOD1 G93A mice, a transgenic animal model of ALS (Kieran et al 2004;Goloubinoff and De Los Rios 2007;Kalmar et al 2008Kalmar et al , 2014McGoldrick et al 2013;Poppe et al 2014). Arimoclomol is a co-inducer of Hsps that prolongs the binding of activated HSF1 to heat shock elements (HSEs) in the promoter regions of heat shock genes (Hargitai et al 2003;Kieran et al 2004;Kalmar et al 2014).…”

“…Arimoclomol is a co-inducer of Hsps that prolongs the binding of activated HSF1 to heat shock elements (HSEs) in the promoter regions of heat shock genes (Hargitai et al 2003;Kieran et al 2004;Kalmar et al 2014). Interestingly, arimoclomol is currently in human clinical trials for ALS (ClinicalTrials.gov identifier: NCT00706147) and is well tolerated in ALS patients up to 300 mg/day (Genc and Ozdinler 2013).…”