Free radical-induced chitosan depolymerized products protect calf thymus DNA from oxidative damage.

Low molecular weight chitosan (LMWC) and chitooligosaccharides (COs), obtained by persulfate-induced depolymerization of chitosan showed scavenging of OH. and O2.- radicals and offered protection against calf thymus DNA damage. Over 85% inhibition of free radicals and DNA protection were observed. LMWC (0.05 micromol) showed a strong inhibitory activity compared to COs (3.6 micromol). Further, LMWC showed calf thymus DNA condensation reversibly giving stability, as evident from CD, TEM and melting curves (Tm). A fluorescence study suggests the binding of LMWC in the minor groove, forming H-bonds to the backbone phosphates without distorting the double helix structure.

Revisiting Metal Toxicity in Neurodegenerative Diseases and Stroke: Therapeutic Potential.

Excessive accumulation of pro-oxidant metals, observed in affected brain regions, has consistently been implicated as a contributor to the brain pathology including neurodegenerative diseases and acute injuries such as stroke. Furthermore, the potential interactions between metal toxicity and other commonly associated etiological factors, such as misfolding/aggregation of amyloidogenic proteins or genomic damage, are poorly understood. Decades of research provide compelling evidence implicating metal overload in neurological diseases and stroke. However, the utility of metal toxicity as a therapeutic target is controversial, possibly due to a lack of comprehensive understanding of metal dyshomeostasis-mediated neuronal pathology. In this article, we discuss the current understanding of metal toxicity and the challenges associated with metal-targeted therapies.

Increased expression of the gamma-secretase components presenilin-1 and nicastrin in activated astrocytes and microglia following traumatic brain injury.

Gamma-secretase is an aspartyl protease composed of four proteins: presenilin (PS), nicastrin (Nct), APH1, and PEN2. These proteins assemble into a membrane complex that cleaves a variety of substrates within the transmembrane domain. The gamma-secretase cleavage products play an important role in various biological processes such as embryonic development and Alzheimer's disease (AD). The major role of gamma-secretase in brain pathology has been linked to AD and to the production of the amyloid beta-peptide. However, little is known about the possible role of gamma-secretase following acute brain insult. Here we examined by immunostaining the expression patterns of two gamma-secretase components, PS1 and Nct, in three paradigms of brain insult in mice: closed head injury, intracerebroventricular injection of LPS, and brain stabbing. Our results show that in naïve and sham-injured brains expression of PS1 and Nct is restricted mainly to neurons. However, following insult, the expression of both proteins is also observed in nonneuronal cells, consisting of activated astrocytes and microglia. Furthermore, the proteins are coexpressed within the same astrocytes and microglia, implying that these cells exhibit an enhanced gamma-secretase activity following brain damage. In view of the important role played by astrocytes and microglia in brain disorders, our findings suggest that gamma-secretase may participate in brain damage and repair processes by regulating astrocyte and microglia activation and/or function.

First evidence on induced topological changes in supercoiled DNA by an aluminium D-aspartate complex.

Aluminium is a debatable and suspected etiological factor in neurodegenerative disorders. Aluminium-amino acid complexes also play an important role in the complex biology of the metal. Recent reports indicate the presence of D-aspartate and D-glutamate in aging brain, human breast tumors, core amyloid plaques and neurofibrillary tangles of Alzheimer's brain. This stereoinversion from the L- to the D-enantiomer is enhanced by Al. Further, the observation that Al is localized in the chromatin region encouraged the present study of the interaction of Al-amino acid complexes with DNA. This study used circular dichroism of supercoiled DNA and showed that Al- D-Asp caused a native B-DNA to C-DNA conformational change, while Al- L-Asp, Al- L-Glu and Al- D-Glu did not alter the native B-DNA conformation. This differential DNA binding property of Al-amino acid complexes is assigned to the stereoisomerism and chirality of the complexes. Interestingly, polyamines like spermine further induced an asymmetric condensation of the "limit C-motif" induced by Al- D-Asp to a Psi-DNA. The results were supported by computer modeling, gel studies and ethidium bromide binding. We also propose a mechanism of Al- D-Asp binding and its ability to modulate DNA topology.