Changes in Drosophila mitochondrial proteins following chaperone-mediated lifespan extension confirm a role of Hsp22 in mitochondrial UPR and reveal a mitochondrial localization for cathepsin D.

Hsp22 is a small mitochondrial heat shock protein (sHSP) preferentially up-regulated during aging in Drosophila melanogaster. Its developmental expression is strictly regulated and it is rapidly induced in conditions of stress. Hsp22 is one of the few sHSP to be localized inside mitochondria, and is the first sHSP to be involved in the mitochondrial unfolding protein response (UPR(MT)) together with Hsp60, mitochondrial Hsp70 and TRAP1.

Drosophila melanogaster mitochondrial Hsp22: a role in resistance to oxidative stress, aging and the mitochondrial unfolding protein response.

Aging is characterized by the accumulation of dysfunctional mitochondria. Since these organelles are involved in many important cellular processes, different mechanisms exist to maintain their integrity. Among them is the mitochondrial unfolding protein response, which triggers the expression of a set of proteins aimed at re-establishing mitochondrial homeostasis.

APP/SOD1 overexpressing mice present reduced neuropathic pain sensitivity.

There are controversies regarding pain expression in mentally disabled people, including Down syndrome patients. The aim of this study was to examine neuropathic pain-related behavior and peripheral nerve regeneration in mouse model of Down syndrome. Sciatic nerves of double transgenic mice, overexpressing both amyloid precursor protein (APP) and Cu/Zn superoxide dismutase (SOD1) genes, and FVB/N wild type mice were transected and immediately resutured.

Protection from aging by small chaperones: A trade-off with cancer?

Aging is a complex process accompanied by a decreased capacity of cells to cope with random molecular damages. Damaged proteins can form aggregates and have cytotoxic properties, a feature of many age-associated diseases. Small Hsps are chaperones involved in the refolding and/or disposal of protein aggregates.

APP overexpression prevents neuropathic pain and motoneuron death after peripheral nerve injury in mice.

Despite general capacity of peripheral nervous system to regenerate, peripheral nerve injury is often followed by incomplete recovery of function and sometimes burdened by neuropathic pain. Amyloid precursor protein (APP) was suggested to play a role in neuronal growth, however, its role in peripheral nerve repair was not studied. The aim of this study was to examine the role of APP overexpression in peripheral nerve regeneration and neuropathic pain-related behavior in mice.

Increased heart rate variability in mice overexpressing the Cu/Zn superoxide dismutase.

Cu/Zn superoxide dismutase (SOD1) is implicated in various pathological conditions including Down's syndrome, neurodegenerative diseases, and afflictions of the autonomic nervous system (ANS). To assess the SOD1 contribution to ANS dysfunction, especially its influence on cardiac regulation, we studied the heart rate variability (HRV) and cardiac arrhythmias in conscious 12-month-old male and female transgenic mice for the human SOD1 gene (TghSOD1). TghSOD1 mice presented heart rate reduction as compared with control FVB/N individuals.

Overexpression of copper/zinc-superoxide dismutase in transgenic mice markedly impairs regeneration and increases development of neuropathic pain after sciatic nerve injury.

Despite the general capacity of peripheral nervous system to regenerate, peripheral nerve injury is often followed by incomplete recovery of function, sometimes with the burden of neuropathic pain. The mechanisms of both regeneration and nociception have not been clarified, but it is known that inflammatory reactions are involved. Cu/Zn-superoxide dismutase (SOD1) is an important scavenger protein that acts against oxidative stress.

Oxidized SOD1 alters proteasome activities in vitro and in the cortex of SOD1 overexpressing mice.

Premature ageing, one of the characteristics of Down syndrome (DS), may involve oxidative stress and impairment of proteasome activity. Transgenic mice overexpressing the human copper/zinc superoxide dismutase (SOD1) gene are one of the first murine models for DS and it has been shown that SOD1 overexpression might be either deleterious or beneficial. Here, we show a reduction in proteasome activities in the cortex of SOD1 transgenic mice and an associated increase in the content of oxidized SOD1 protein.

Proteome analysis in hippocampus of mice overexpressing human Cu/Zn-superoxide dismutase 1.

Cu/Zn-superoxide dismutase 1 (SOD1), encoded on chromosome 21, is a key enzyme in metabolism of oxygen free radicals and oxidative stress. Transgenic mice overexpressing human SOD1 (Tg-hSOD1) are useful model for Down syndrome (trisomy 21) and familial amyotrophic lateral sclerosis (ALS). It was shown recently that Tg-hSOD1 mice develop a characteristic set of neurodegenerative changes in hippocampus and we therefore decided to study differential protein expression patterns, constructing a mouse hippocampal proteome map using two-dimensional electrophoresis (2-DE) with in-gel digestion of spots followed by matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF) identification and quantitatively compared protein profiles between non-transgenic mice, hemizygous and homozygous Tg-hSOD1 mice.

Aberrant neuronal and mitochondrial proteins in hippocampus of transgenic mice overexpressing human Cu/Zn superoxide dismutase 1.

Mutations of Cu/Zn superoxide dismutase 1 (SOD1), a metalloenzyme catalyzing the conversion of superoxide anion to hydrogen peroxide (H(2)O(2)), are linked to motor neuron degeneration. Transgenic mouse strains overexpressing wild-type human SOD1 (Tg-SOD1) were shown to have mitochondrial swelling, vacuolization, or learning and memory deficits and are widely used for biochemical, genetic, and cognitive studies; this, along with the advent of advanced proteomic methods, made us investigate protein expression in hippocampus. Hippocampal tissues of wild-type, hemizygous, and homozygous Tg-SOD1 mice were isolated and used for two-dimensional gel electrophoresis with subsequent matrix-assisted laser desorption/ionization-time of flight identification.

In vitro evaluation and biodistribution of a 99mTc-labeled anti-VEGF peptide targeting neuropilin-1.

Neuropilins (NRP) are receptors of angiogenic vascular endothelial growth factor (VEGF). Their overexpression was correlated with tumor angiogenesis and growth suggesting that their specific targeting could provide a new marker of tumor progression. Here, we observed in vitro that new (99m)Tc-labeled derivative of anti-VEGF heptapeptide, ATWLPPR, binds to NRP1 but not to NRP2.

Altered expression of hypothetical proteins in hippocampus of transgenic mice overexpressing human Cu/Zn-superoxide dismutase 1.

BACKGROUND: Cu/Zn-superoxide dismutase 1 (SOD1), encoded on chromosome 21, is a key enzyme in the metabolism of reactive oxygen species (ROS) and pathogenetically relevant for several disease states including Down syndrome (DS; trisomy 21). Systematically studying protein expression in human brain and animal models of DS we decided to carry out "protein hunting" for hypothetical proteins, i.e.