Hydrogen sulfide in longevity and pathologies: Inconsistency is malodorous.

Hydrogen sulfide (H2S) is one of the biologically active gases (gasotransmitters), which plays an important role in various physiological processes and aging. Its production in the course of methionine and cysteine catabolism and its degradation are finely balanced, and impairment of H2S homeostasis is associated with various pathologies. Despite the strong geroprotective action of exogenous H2S in C. elegans, there are controversial effects of hydrogen sulfide and its donors on longevity in other models, as well as on stress resistance, age-related pathologies and aging processes, including regulation of senescence-associated secretory phenotype (SASP) and senescent cell anti-apoptotic pathways (SCAPs). Here we discuss that the translation potential of H2S as a geroprotective compound is influenced by a multiplicity of its molecular targets, pleiotropic biological effects, and the overlapping ranges of toxic and beneficial doses. We also consider the challenges of the targeted delivery of H2S at the required dose. Along with this, the complexity of determining the natural levels of H2S in animal and human organs and their ambiguous correlations with longevity are reviewed.

Synthetic Fragment of Receptor for Advanced Glycation End Products Prevents Memory Loss and Protects Brain Neurons in Olfactory Bulbectomized Mice.

Activation of receptor for advanced glycation end products (RAGE) plays an essential role in the development of Alzheimer's disease (AD). It is known that the soluble isoform of the receptor binds to ligands and prevents negative effects of the receptor activation. We proposed that peptide fragments from RAGE prevent negative effects of the receptor activation during AD neurodegeneration. We have synthesized peptide fragments from surface-exposed regions of RAGE. Peptides were intranasally administrated into olfactory bulbectomized (OBX) mice, which developed some characteristics similar to AD neurodegeneration. We have found that only insertion of fragment (60-76) prevents the memory of OBX mice. Immunization of OBX mice with peptides showed that again only (60-76) peptide protected the memory of animals. Both intranasal insertion and immunization decreased the amyloid-ß (Aß) level in the brain. Activity of shortened fragments of (60-76) peptide was tested and showed only the (60-70) peptide is responsible for manifestation of activity. Intranasal administration of (60-76) peptide shows most protective effect on morpho-functional characteristics of neurons in the cortex and hippocampal areas. Using Flu-(60-76) peptide, we revealed its penetration in the brain of OBX mice as well as colocalization of Flu-labeled peptide with Aß in the brain regions in transgenic mice. Flu-(60-76) peptide complex with trimer of Aß was detected by SDS-PAGE. These data indicate that Aß can be one of the molecular target of (60-70) peptide. These findings provide a new peptide molecule for design of anti-AD drug and for investigation of RAGE activation ways in progression of AD neurodegeneration.