Heat Shock Proteins and Amateur Chaperones in Amyloid-Beta Accumulation and Clearance in Alzheimer’s Disease

The pathologic lesions of Alzheimer’s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular or extracellular misfolded proteins. The amyloid-β (Aβ) protein accumulates extracellularly in senile plaques and cerebral amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. “Professional chaperones”, such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent aggregation. “Amateur” chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions of AD, but may also be involved in conformational changes of Aβ, and in the clearance of Aβ from the brain via phagocytosis or active transport across the blood–brain barrier. Thus, both professional and amateur chaperones may be involved in the aggregation, accumulation, persistence, and clearance of Aβ and tau and in other Aβ-associated reactions such as inflammation associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention

Interaction between Glyglu and Ca2+, Pb2+, Cd2+ and Zn2+ in solid state and aqueous solution. Crystal structures of poly[aqua-1,2-kappa-O-di[lead(glygluH)]bis(perchlorate)] and poly[bisglycylglutamic-cadmium(II) tetrahydrate]

Glycylglutamic acid (GEH(2)) is a peptide usually present in calcium binding sites. The interaction between the peptide and the cations Ca2+ Pb2+, Cd2+, and Zn in aqueous solution and in the solid state is described. Six compounds were isolated with different protonation states of the ligand. Potentiometric equilibrium studies, C-13 and Cd-111 solid state CP MAS NMR and IR spectroscopy were performed. Two crystal structures are reported: [Pb(GEH)(H2O)](1/2)]ClO4 and [Cd(GEH)(2)].3H(2)O. Both constitute 3D polymers, where only carboxylate groups are coordinated to the cations. The crystalline lead compound shows a hemidirected coordination sphere due to its stereochemically active lone pair. In deprotonated derivatives, it is possible to assign a metal-amino interaction to a far IR signal (340-370 cm(-1)). (C) 2002 Elsevier Science B.V. All rights reserved

Complexation of lead(II) by L-aspartate: crystal structure of polymeric Pb(aspH) (NO3)

Two lead compounds containing the aspartate ligand are described, with compositions Pb(aspH)NO3 and Pb(asp). The crystal structure of the first shows it is a three-dimensional polymer in which each lead atom is coordinated to six oxygen atoms, five from carboxyl groups and one from a nitrate ion, For Pb(asp), spectroscopic data suggest the presence of Pb-NH2 interaction. (C) 2000 Elsevier Science Ltd All rights reserved

Chikungunya Virus Pathogenesis and Immunity

International audienceChikungunya virus (CHIKV) is an arbovirus associated with acute and chronic arthralgia that re-emerged in the Indian Ocean islands in 2005–2006 and is currently responsible for the ongoing outbreaks in the Caribbean islands and the Americas. We describe here the acute and chronic clinical manifestations of CHIKV in patients that define the disease. We also review the various animal models that have been developed to study CHIKV infection and pathology and further strengthened the understanding of the cellular and molecular mechanisms of CHIKV infection and immunity. A complete understanding of the immunopathogenesis of CHIKV infection will help develop the needed preventive and therapeutic approaches to combat this arbovirosis

Complement factors C1q, C3 and C5 in brain and serum of mice with cerebral malaria

<p>Abstract</p> <p>Background</p> <p>The patho-mechanisms leading to brain damage due to cerebral malaria (CM) are yet not fully understood. Immune-mediated and ischaemic mechanisms have been implicated. The role of complement factors C1q, C3 and C5 for the pathogenesis of CM were investigated in this study.</p> <p>Methods</p> <p>C57BL/6J mice were infected with <it>Plasmodium berghei ANKA </it>blood stages. The clinical severity of the disease was assessed by a battery of 40 standardized tests for evaluating neurological functions in mice. Brain homogenates and sera of mice with CM, infected animals without CM and non-infected control animals were analyzed for C1q, C3 and C5 up-regulation by Western blotting.</p> <p>Results</p> <p>Densitometric analysis of Western blots of brain homogenates yielded statistically significant differences in the levels of C1q and C5 in the analyzed groups. Correlation analysis showed a statistically significant association of C1q and C5 levels with the clinical severity of the disease. More severely affected animals showed higher levels of C1q and C5. No differences in complement levels were observed between frontal and caudal parts of the brain. Densitometric analysis of Western blot of sera yielded statistically lower levels of C1q in infected animals without CM compared to animals of the control group.</p> <p>Conclusion</p> <p>The current study provides direct evidence for up-regulation of complement factors C1q and C5 in the brains of animals with CM. Local complement up-regulation is a possible mechanism for brain damage in experimental cerebral malaria.</p