A cell-permeable N-aryl benzimidazole (NAB) compound that protects against α-synuclein (α-syn) toxicity in yeast (0.625 to 10 µM), wt human α-syn-expressing C. elegans dopaminergic (DA) neurons (10 µM), human A53T α-syn-expressing rat DA neurons (0.1 µM), as well as in human neurons differentiated from iPSCs derived from Parkinson′s disease (PD) patients carrying either AT53T α-syn or an α-syn triplication (5 to 40 µM) by restoring Nedd4 (mammalian)/Rsp5 (yeast) E3 ligase-dependent processes, including ER-to-Golgi, plasma membrane- and Golgi-to-vacuole/lysosome trafficking events, reducing α-syn-caused nitrosative and ER stress. NAB2 is also reported to inhibit the growth, but not viability, of non-α-syn-expressing yeast via the same mechanism of action (MOA) albeit at a lower potency (GI40 = 20.5 µM vs. EC40 = 4.5 µM against α-syn toxicity). Although the exact molecular mechanism is yet unknown, NAB2 does not affect cellular α-syn level or Nedd4/Rsp5 ligase activity.
A cell-permeable N-aryl benzimidazole (NAB) compound that protects against α-synuclein (α-syn) toxicity in yeast (0.625 to 10 µM), wt human α-syn-expressing C. elegans dopaminergic neurons (10 µM), human A53T α-syn-expressing rat DA neurons (0.1 µM), as well as in Parkinson′s disease patients-derived neurons carrying AT53T α-syn or an α-syn triplication (5 to 40 µM) by restoring Nedd4 (mammalian)/Rsp5 (yeast) E3 ligase-dependent trafficking events, reducing α-syn-caused nitrosative and ER stress without affecting cellular α-syn level or Nedd4/Rsp5 ligase activity.
A cell-permeable compound that protects against alpha-synuclein toxicity.
Biochem/physiol Actions
Cell permeable: yes
Caution
NAB2 is moderately hydrophobic (clogP ~5.2)and can precipitate out of solution if added directly to cell culture or yeast media. Care should therefore be taken to optimize solubility and guard against false negative results caused by irrecoverable precipitation of the compound. Please refer to the Recommended Reaction Conditions above for details.
Warning
Toxicity: Standard Handling (A)
Reconstitution
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Other Notes
Tardiff, D.F., et al. 2013. Science342, 979. Chung, C.Y., et al. 2013. Science342, 983.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Storage Class
11 - Combustible Solids
wgk_germany
WGK 3
flash_point_f
Not applicable
flash_point_c
Not applicable
Certificates of Analysis (COA)
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