The role of Cdk5-mediated Drp1 phosphorylation in Aß1-42 induced mitochondrial fission and neuronal apoptosis.

Alzheimer's disease, one of the most common neurodegenerative diseases, is pathologically characterized by Amyloid beta containing plaques and neurofibrillary tangles. Amyloid beta (Aß) induces neuronal apoptosis through the intracellular Ca2+ increase, subsequent hyperactivation of cyclin-dependent kinase 5 (Cdk5) and mitochondrial abnormality. Recently, Cdk5 was identified as an upstream regulator of mitochondrial fission during neuronal apoptosis, but the underlying mechanism remains unclear. Here, in vitro phosphorylation assays showed that Cdk5 could phosphorylate the recombinant Drp1 at Serine 579. Aß1-42 stimulation increased the phosphorylation level of Drp1 at Serine 579 in mouse cortical neurons. Cdk5 inhibitor roscovitine and knockdown of Cdk5 by a lentiviral vector expressing shRNA targeting Cdk5 (Lenti-Cdk5-shRNA) efficiently prevented Aß1-42 induced Drp1 phosphorylation in neurons. In addition, Aß1-42 stimulation induced markedly mitochondrial fission in neurons. Roscovitine, Lenti-Cdk5-shRNA and expression of phospho-defect mutatant GFP-Drp1-S579A in neurons attenuated Aß1-42 induced mitochondrial fission, whereas expression of phospho-mimetic mutant GFP-Drp1-S579D alone resulted in mitochondiral fission similar to Aß1-42 stimulation. Moreover, Roscovitine and Lenti-Cdk5-shRNA suppressed the cleavage of caspase-3 and protected neurons against Aß1-42 induced neuronal apoptosis.Thus, our data indicate that Drp1 is a direct target of Cdk5, and Cdk5-mediated phosphorylation of Drp1 at Serine 579 regulates Aß1-42 induced mitochondrial fission and neuronal toxicity.

catena-Poly[1,4-dihydroxy-1,4-diazoniabicyclo[2.2.2]octane [aquatri-µ-chlorido-trichloridodicuprate(II)]].

The title compound, {(C6H14N2O2)[Cu2Cl6(H2O)]}n, consists of 1,4-dihydroxy-1,4-diazoniabicyclo[2.2.2]octane dications and one-dimensional inorganic anionic {[Cu2Cl6(H2O)](2-)}n chains in which both five-coordinate [CuCl3(H2O)](-) and five-coordinate [CuCl3](-) units exist. These two distinct type of unit are linked together by one chloride ion and are bridged across centres of inversion to further units of their own type through two chloride ions, giving rise to novel polymeric zigzag chains parallel to the c axis. The chains are connected by O-H···Cl hydrogen bonds to produce R2(4)(16) ring motifs, resulting in two-dimensional layers parallel to the ac plane. These layers are linked into a three-dimensional framework with the organic cations via O-H···Cl hydrogen bonds. Hydrogen bonding between the chains, and between the chains and the organic cations, provides stability to the crystal structure.

A potential molecular ferroelectric material: poly[[bis(1-aza-4-azoniabicyclo[2.2.2]octane)di-µ3-chlorido-tetra-µ2-chlorido-dichloridotricadmium(II)] dihydrate].

The title compound, {[Cd3(C6H13N2)2Cl8]·2H2O}n, consists of pendant protonated cationic diamine ligands bonded to an anionic one-dimensional coordination polymer chloridocadmate scaffold. Each coordination chain features two kinds of Cd(II) centre, each with distorted octahedral coordination geometry. One Cd(II) cation lies on a centre of inversion and is coordinated by six bridging chloride ligands, while the other is coordinated by four bridging chloride ligands, one terminal chloride ligand and a 1-aza-4-azoniabicyclo[2.2.2]octane aza N atom. This gives a reversible corner-sharing half-cubic linear polymer that lies along the crystallographic a direction. The chains interact through hydrogen bonding with solvent water, with each water molecule accepting one N-H...O interaction from a cation and donating to two O-H...Cl interactions with anionic chains, thus linking three separate chains and completing the packing structure.

1-[(Pyridin-3-yl)(pyrrolidin-1-yl)meth-yl]naphthalen-2-ol.

The title compound, C(20)H(20)N(2)O, was synthesized by a solvent-free one-pot three-component domino reaction of naph-tha-len-2-ol, nicotinaldehyde and pyrrolidine. The dihedral angle between the naphthalene ring system and the pyridine ring is 74.22 (6)°. The pyrrolidine ring assumes an envelope conformation with the N atom as the flap. An intra-molecular O-H⋯N hydrogen bond stabilizes the mol-ecular conformation.