An extensive phenotypic characterization of the hTNFalpha transgenic mice.

Background: Tumor necrosis factor alpha (TNFalpha) is implicated in a wide variety of pathological and physiological processes, including chronic inflammatory conditions, coronary artery disease, diabetes, obesity, and cachexia. Transgenic mice expressing human TNFalpha (hTNFalpha) have previously been described as a model for progressive rheumatoid arthritis. In this report, we describe extensive characterization of an hTNFalpha transgenic mouse line.

In vitro and in vivo pharmacological profile of AS057278, a selective d-amino acid oxidase inhibitor with potential anti-psychotic properties.

Non-competitive N-methyl-d-aspartate (NMDA) blockers induce schizophrenic-like behavior in healthy volunteers and exacerbate symptomatology in schizophrenic patients. Hence, a compound able to enhance NMDA neurotransmission by increasing levels of d-serine, an endogenous full agonist at the glycine site of the NMDA receptors, could have anti-psychotic activity. One way to increase d-serine levels is the inhibition of d-amino acid oxidase (DAAO), the enzyme responsible for d-serine oxidation.

ABAD enhances Abeta-induced cell stress via mitochondrial dysfunction.

Amyloid-beta peptide (Abeta) binding alcohol dehydrogenase (ABAD), an enzyme present in neuronal mitochondria, is a cofactor facilitating Abeta-induced cell stress. We hypothesized that ABAD provides a direct link between Abeta and cytotoxicity via mitochondrial oxidant stress. Neurons cultured from transgenic (Tg) mice with targeted overexpression of a mutant form of amyloid precursor protein and ABAD (Tg mAPP/ABAD) displayed spontaneous generation of hydrogen peroxide and superoxide anion, and decreased ATP, as well as subsequent release of cytochrome c from mitochondria and induction of caspase-3-like activity followed by DNA fragmentation and loss of cell viability.

Resistance of alpha -synuclein null mice to the parkinsonian neurotoxin MPTP.

Parkinson's disease (PD) is most commonly a sporadic illness, and is characterized by degeneration of substantia nigra dopamine (DA) neurons and abnormal cytoplasmic aggregates of alpha-synuclein. Rarely, PD may be caused by missense mutations in alpha-synuclein. MPTP, a neurotoxin that inhibits mitochondrial complex I, is a prototype for an environmental cause of PD because it produces a pattern of DA neurodegeneration that closely resembles the neuropathology of PD.