A copper chaperone–mimetic polytherapy for SOD1-associated amyotrophic lateral sclerosis

Abstract

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Assessment of protein inclusions in cultured cells using automated image analysis

“…For examples of this method in action to detect protein inclusions in cells, see Figures 1 , 2 , and 3 for processed and analyzed data in McAlary et al. (2022) .…”

“…This protocol is highly scalable and can be applied to a few images or large datasets. For complete details on the use and execution of this protocol, please refer to McAlary et al. (2022) .…”

“…For complete details on the use and execution of this protocol, please refer to McAlary et al. (2022) .…”

Is Dutasteride a Therapeutic Alternative for Amyotrophic Lateral Sclerosis?

“…For example, in the SOD1G93A mouse model, mutated-protein accumulation in the mitochondria and cytosol causes impaired energy metabolism and OS in the lungs, with the lower activity of antioxidant enzymes, such as glutathione reductase or catalase [ 55 ]. In addition to the loss of function of antioxidant enzymes, mutations in SOD1 reduce the protein-folding stability through the disruption of metal binding and/or disulfide-bond formation, resulting in misfolding, aggregation and ultimately cell toxicity [ 56 ].…”

Cells Overexpressing ALS-Associated SOD1 Variants Are Differentially Susceptible to CuATSM-Associated Toxicity

“…8,13 As such, facilitating the PTMs that assist with SOD1 maturation and proper folding has been identified as an avenue for therapeutic treatment. 7,14,15 Diacetylbis(N(4)-methylthiosemicarbazonato)copper(II) (CuATSM) is a Cu-based low molecular weight compound that can readily cross the blood-brain barrier and has been recently used to rescue deficits in both cell and mouse models of fALS. 16−21 Oral administration of CuATSM has been shown to delay disease onset, slow disease progression and extend lifespan in multiple SOD1 mouse models.…”