The guiding hypothesis directing the research to be described was that a combination of the two factors would exacerbate the decline in the DA transmitter system function that occurs during aging. The results obtained were consistent with the well-established aging-related decline in function and structure of neurons utilizing DA as a transmitter and motor function, and extended knowledge by establishing that the genetic reduction of Gdnf exacerbated these aging related changes. Thus, GDNF reduction appears to increase the vulnerability of the check details DA neurons to the many different challenges associated with the aging process. Assessment of methamphetamine effects on young Gdnf(+/-) mice indicated that reduced GDNF availability

increased the vulnerability of DA systems to this well-established neurotoxin. The work discussed in this review is consistent with earlier work demonstrating the importance of GDNF for maintenance of DA neurons and also provides a novel model for progressive DA degeneration and motor dysfunction. (C) 2009 Elsevier Ltd. All rights reserved.”
“Paramyxoviruses initiate entry through the concerted action of the tetrameric attachment glycoprotein

(HN, H, or G) and the trimeric fusion glycoprotein see more (F). The ectodomains of HN/H/G contain a stalk region important for oligomeric stability and for the F triggering resulting in membrane fusion. Paramyxovirus HN, H, and G form a dimer-of-dimers consisting of disulfide-linked dimers through their stalk domain cysteines. The G attachment protein stalk domain of the highly pathogenic Nipah virus (NiV) contains a distinct but uncharacterized cluster of three cysteine residues (C146, C158, C162). On the basis of a panoply of assays, we report that C158 and C162 of NiV-G likely mediate covalent subunit dimerization, while C146 mediates the stability of higher-order oligomers. learn more For HN or H, mutation of stalk cysteines attenuates but does not abrogate the ability to trigger fusion.

In contrast, the NiV-G stalk cysteine mutants were completely deficient in triggering fusion, even though they could still bind the ephrinB2 receptor and associate with F. Interestingly, all cysteine stalk mutants exhibited constitutive exposure of the Mab45 receptor binding-enhanced epitope, previously implicated in F triggering. The enhanced binding of Mab45 to the cysteine mutants relative to wild-type NiV-G, without the addition of the receptor, implicates the stalk cysteines in the stabilization of a pre-receptor-bound conformation and the regulation of F triggering. Sequence alignments revealed that the stalk cysteines were adjacent to a proline-rich microdomain unique to the Henipavirus genus. Our data propose that the cysteine cluster in the NiV-G stalk functions to maintain oligomeric stability but is more importantly involved in stabilizing a unique microdomain critical for triggering fusion.”
“A number of addictions have been linked with decreased striatal dopamine (DA) receptor availability and DA release.