Human SNPH blocking peptide

Thirteen organotin(IV) and low valent complexes of group 14 (Ge, Sn, Pb) containing L-NO ligand(s) (where L-NO is 2-(N, N-dimethylaminomethyl) phenolate) were synthesized and its structure described by NMR techniques in solution and X-ray techniques in the solid state (for L2(NO)SnPh(2), (L2SnCl2)-Sn-NO, (L2Ge)-Ge-NO and (LSnCl)-Sn-NO which forms a dimer). Structures and properties of prepared species have been compared with previously published germanium and tin compounds containing -OCH2CH2NMe2 as O,N- or L-CN (where L-CN is 2-(N, N-dimethylaminomethyl) phenyl) as C, N-chelating ligands. The solid state structures containing L-NO ligand(s) reveal much stronger intramolecular N -> Sn coordination than complexes containing latter two ligands. (C) 2013 Elsevier B.V. All rights reserved.

Chronic mitochondrial stress is a central problem associated with neurodegenerative diseases. Early removal of defective mitochondria from axons constitutes a critical step of mitochondrial quality control. Here we investigate axonal mitochondrial response to mild stress in wild-type neurons and chronic mitochondrial defects in Amytrophic Lateral Sclerosis (ALS)- and Alzheimer's disease (AD)-linked neurons. We show that stressed mitochondria are removed from axons triggered by the bulk release of mitochondrial anchoring protein syntaphilin via a new class of mitochondria-derived cargos independent of Parkin, Drp1, and autophagy. Immuno-electron microscopy and super-resolution imaging show the budding of syntaphilin cargos, which then share a ride on late endosomes for transport toward the soma. Releasing syntaphilin is also activated in the early pathological stages of ALS- and AD-linked mutant neurons. Our study provides new mechanistic insights into the maintenance of axonal mitochondrial quality through SNPH-mediated coordination of mitochondrial stress and motility before activation of Parkin-mediated mitophagy.