Details

Autor(en) / Beteiligte

• McAlary, Luke
• Yerbury, Justin

Titel

Strategies to promote the maturation of ALS-associated SOD1 mutants: small molecules return to the fold

Ist Teil von

• Neural regeneration research, 2019-09, Vol.14 (9), p.1511-1512

Ort / Verlag

India: Wolters Kluwer India Pvt. Ltd

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• (Cu)IIATSM (CuATSM) promotes the proper folding of familial amyotrophic lateral sclerosis (fALS)-associated copper, zinc superoxide dismutase (SOD1): ALS is a progressive neurodegenerative disease that affects motor neurons in the cortex and spinal cord, resulting in paralysis and ultimately death. Recently, a copper (Cu)-based small molecule called CuATSM was found to be effective at treating multiple transgenic mouse models expressing human SOD1-fALS protein (Soon et al., 2011; Roberts et al., 2014). [...]the selenium-based antioxidant compound ebselen was shown to significantly increase the dimer-binding affinity of SOD1-fALS mutants in vitro and exert minimal toxicity to cultured cells (Capper et al., 2018). [...]ebselen may prove to be a useful lead compound in this class of drug, as in-cell nuclear magnetic resonance previously showed that cells expressing G93A or A4V SOD1 in the presence of ebselen were fully disulfide oxidized (Capper et al., 2018), whereas ~95% of the SOD1 expressed in the absence of ebselen existed in a disulfide reduced state.