Stephen Strittmatter on Ablation of cellular prion protein does not ameliorate abnormal neural network activity or cognitive dysfunction in the J20 line of human amyloid precursor protein transgenic mice.

COMMENT A growing body of literature supports a key role of cellular prion protein (PrPc) in Alzheimer's pathophysiology. Recent reports have demonstrated that endogenous Aβ oligomers from both mouse and human AD brain bind PrPc, and that PrPc is required fo

Lee J. Martin on Misfolded SOD1 associated with motor neuron mitochondria alters mitochondrial shape and distribution prior to clinical onset.

COMMENT My quick impression is that this work by Vande Velde et al. confirms many earlier studies suggesting that mitochondrial pathobiology may have an important role in the pathogenesis of ALS in mouse models. It is exciting and encouraging that many of the ima

Lee J. Martin

Johns Hopkins University School of Medicine
Baltimore, United States

Torleif Hard on Rationally designed turn promoting mutation in the amyloid-β peptide sequence stabilizes oligomers in solution.

COMMENT Pande's group introduces a D-proline at position 37 of the Aβ sequence, which is incompatible with the fibril cross-β structure. This will certainly keep their peptide away from the fibril state, stopping aggregation at the oligomer level. In these o

Virgil Muresan on LRAD3, a novel low-density lipoprotein receptor family member that modulates amyloid precursor protein trafficking.

COMMENT There is no question that the complex processing of amyloid-β precursor protein (APP), via at least two intensely studied pathways (α- and β-secretase cleavage) that are relevant to Alzheimer’s disease (AD), occurs during APP’s still insufficiently unders

PAPER Dries DR, Yu G

Rip exposed: how ectodomain shedding regulates the proteolytic processing of transmembrane substrates.

Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14737-8. PubMed: 19717451

PAPER Li X, Wang B, Feng L, Kang H, Qi Y, Wang J, Shi Y

Cleavage of RseA by RseP requires a carboxyl-terminal hydrophobic amino acid following DegS cleavage.

Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14837-42. PubMed: 19706448

PAPER Hayashi I, Takatori S, Urano Y, Miyake Y, Takagi J, Sakata-Yanagimoto M, Iwanari H, Osawa S, Morohashi Y, Li T, Wong PC, Chiba S, Kodama T, Hamakubo T, Tomita T, Iwatsubo T

Neutralization of the γ-secretase activity by monoclonal antibody against extracellular domain of nicastrin.

Oncogene. 2011 Jul 4; PubMed: 21725355

Loretta Vosk

Seattle, United States

Gang Yu on Mutations in nicastrin protein differentially affect amyloid beta-peptide production and Notch protein processing.

COMMENT Karlstrom, Naslund, and colleagues now provide evidence that two conserved cysteine residues (C213 and C230) in the nicastrin ectodomain can differentially affect γ-secretase processing of APP and Notch. The authors showed that mutating these residues res

Grace Stutzmann on Constitutive cAMP response element binding protein (CREB) activation by Alzheimer's disease presenilin-driven inositol trisphosphate receptor (InsP3R) Ca2+ signaling.

COMMENT The prominence of early/pre-symptomatic calcium signaling disruptions in mutant presenilin (PS)-expressing neurons has been well established in the AD field, but to fortify relevance to the disease process, dysregulated calcium still needs to be transduce

Ellen Melbye Langballe

Norwegian Institute of Public Health
Oslo, Norway

Jeroen Schuermans

Belgium

Hainuo Cheng

Shenzhen, China

Bin Li

LSU Health Science Center-Shreveport
Shreveport, United States