1504588-00-4

alphaSYN-IN-NAB2 is an inhibitor of α-synuclein mutations. It acts by reversing the α-synuclein-induced pathological phenotype in Parkinson's disease cortical neurons and promoting E3 ubiquitin ligase Rsp5/Nedd4-dependent endosomal transport..

NAB2 is a neuroprotectant that targets the small GTPase Rab1a. NAB2 selectively binds to the GDP-bound form of Rab1a and protects multiple cell types from α-synuclein toxicity by increasing Rab1a expression. Rab1a regulates ER-to-Golgi trafficking and mediates endosomal trafficking events of the E3 ubiquitin ligase Rsp5/Nedd4. NAB2 stimulates ubiquitination of related proteins in a Nedd4-dependent manner and rescues α-synuclein-associated trafficking defects associated with early-onset Parkinson's disease[1][2][3].

ChEBI:N-(2-chlorobenzyl)-1-(2,5-dimethylphenyl)benzimidazole-5-carboxamide is an aromatic amide obtained by the formal condensation of the carboxy group of 1-(2,5-dimethylphenyl)benzimidazole-5-carboxylic acid with the amino group of 2-chlorobenzylamine. It is a member of benzimidazoles, an aromatic amide, a monocarboxylic acid amide and a member of monochlorobenzenes.

α-synuclein

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[1] Tardiff DF, et al. Yeast reveal a "druggable" Rsp5/Nedd4 network that ameliorates α-synuclein toxicity in neurons. Science. 2013;342(6161):979-983. DOI:10.1126/science.1245321
[2] Hatstat AK, et al. Chemoproteomic-enabled characterization of small GTPase Rab1a as a target of an N-arylbenzimidazole ligand's rescue of Parkinson's-associated cell toxicity. RSC Chem Biol. 2021 Nov 9;3(1):96-111. DOI:10.1039/d1cb00103e