The hypoxia imaging agent CuII(atsm) is neuroprotective and improves motor and cognitive functions in multiple animal models of Parkinson’s disease

Hung, Lin W.; Villemagne, Victor L.; Cheng, Lesley; Sherratt, Nicki A.; Ayton, Scott; White, Anthony R.; Crouch, Peter J.; Lim, SinChun; Leong, Su Ling; Wilkins, Simon; George, Jessica; Roberts, Blaine R.; Pham, Chi L.L.; Liu, Xiang; Chiu, Francis Chi Keung; Shackleford, David M.; Powell, Andrew K.; Masters, Colin L.; Bush, Ashley I.; O’Keefe, Graeme; Culvenor, Janetta G.; Cappai, Roberto; Cherny, Robert A.; Donnelly, Paul S.; Hill, Andrew; Finkelstein, David I.; Barnham, Kevin J.

doi:10.1084/jem.20112285

Cited by 157 publications

(189 citation statements)

References 96 publications

(136 reference statements)

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“…In line with this, in animal models of PD, Cu II (atsm) improved motor and cognition function and rescued cell loss within substantia nigra by reducing peroxynitrite-driven toxicity and promoting neuroprotection (Ref. 106). …”

Section: Copper Homeostasis and Mitochondrial Dysfunctionmentioning

confidence: 74%

“…Cu II (atsm), which transports Cu(II) throughout the body and delivers it when it reaches oxidative tissues, has shown a therapeutic effect in several animal models of ALS and PD (Refs 52,63,104,(106)(107)(108). In particular, Cu II (atsm) significantly improves locomotor function and increases mouse survival in SOD1-G93A, SOD1-G37R (Refs 52, 104, 107, 108) and TDP-43 (A315 T) mouse models of ALS (Ref.…”

Section: Copper Homeostasis and Mitochondrial Dysfunctionmentioning

confidence: 99%

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Insights into the mechanisms of copper dyshomeostasis in amyotrophic lateral sclerosis

Gil-Bea

Aldanondo

Munáin

et al. 2017

Expert Rev. Mol. Med.

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Amyotrophic lateral sclerosis (ALS) is a severe neuromuscular disease characterised by a progressive loss of motor neurons that usually results in paralysis and death within 2 to 5 years after disease onset. The pathophysiological mechanisms involved in ALS remain largely unknown and to date there is no effective treatment for this disease. Here, we review clinical and experimental evidence suggesting that dysregulation of copper homeostasis in the central nervous system is a crucial underlying event in motor neuron degeneration and ALS pathophysiology. We also review and discuss novel approaches seeking to target copper delivery to treat ALS. These novel approaches may be clinically relevant not only for ALS but also for other neurological disorders with abnormal copper homeostasis, such as Parkinson's, Huntington's and Prion diseases.

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Section: Copper Homeostasis and Mitochondrial Dysfunctionmentioning

confidence: 74%

Section: Copper Homeostasis and Mitochondrial Dysfunctionmentioning

confidence: 99%

Insights into the mechanisms of copper dyshomeostasis in amyotrophic lateral sclerosis

Gil-Bea

Aldanondo

Munáin

et al. 2017

Expert Rev. Mol. Med.

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“…The coppercontaining bis(thiosemicarbazone) compound Cu II GTSM, has been shown to lower Aβ levels, GSK3β activity, and phosphorylated tau levels in cell culture and APP/PS1 transgenic mice [194,219], which accompanied improved cognition in the Y-maze assay. A related compound, Cu II ATSM, was not beneficial to the APP/PS1 transgenic model of AD, but conferred neuroprotection in 4 animal models of PD [220], which is also complicated by copper deficiency [168].…”

Section: Bis(thiosemicarbazone) Ligandsmentioning

confidence: 96%

Biometals and Their Therapeutic Implications in Alzheimer's Disease

2015

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No disease modifying therapy exists for Alzheimer's disease (AD). The growing burden of this disease to our society necessitates continued investment in drug development. Over the last decade, multiple phase 3 clinical trials testing drugs that were designed to target established disease mechanisms of AD have all failed to benefit patients. There is, therefore, a need for new treatment strategies. Changes to the transition metals, zinc, copper, and iron, in AD impact on the molecular mechanisms of disease, and targeting these metals might be an alternative approach to treat the disease. Here we review how metals feature in molecular mechanisms of AD, and we describe preclinical and clinical data that demonstrate the potential for metal-based drug therapy.

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“…2A). ATSM has been developed for tumor imaging and diagnosis and is currently in clinical trials (13)(14)(15). In the absence of copper, ATSM at concentrations of up to 10 M had no apparent inhibitory effect on M. tuberculosis.…”

mentioning

confidence: 99%

Copper-Boosting Compounds: a Novel Concept for Antimycobacterial Drug Discovery

Speer

Shrestha

Bossmann

et al. 2013

Antimicrob Agents Chemother

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The hypoxia imaging agent CuII(atsm) is neuroprotective and improves motor and cognitive functions in multiple animal models of Parkinson’s disease

Abstract: The PET imaging agent CuII(atsm) improves motor and cognitive function in Parkinson’s disease.

Cited by 157 publications

References 96 publications

Insights into the mechanisms of copper dyshomeostasis in amyotrophic lateral sclerosis

Insights into the mechanisms of copper dyshomeostasis in amyotrophic lateral sclerosis

Biometals and Their Therapeutic Implications in Alzheimer's Disease

Copper-Boosting Compounds: a Novel Concept for Antimycobacterial Drug Discovery

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