Antioxidative peptides from food proteins: a review

Psychopharmacology: The Fourth Generation of Progress.

Lead, a systemic toxicant affecting virtually every organ system, primarily affects the central nervous system, particularly the developing brain. Consequently, children are at a greater risk than adults of suffering from the neurotoxic effects of lead. To date, no safe lead-exposure threshold has been identified. The ability of lead to pass through the blood-brain barrier is due in large part to its ability to substitute for calcium ions. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurologic disorders. At the molecular level, lead interferes with the regulatory action of calcium on cell functions and disrupts many intracellular biological activities. Experimental studies have also shown that lead exposure may have genotoxic effects, especially in the brain, bone marrow, liver, and lung cells. Knowledge of the neurotoxicology of lead has advanced in recent decades due to new information on its toxic mechanisms and cellular specificity. This paper presents an overview, updated to January 2009, of the neurotoxic effects of lead with regard to children, adults, and experimental animals at both cellular and molecular levels, and discusses the biomarkers of lead exposure that are useful for risk assessment in the field of environmental health.

/pdf/neurotoxic-effects-and-biomarkers-of-lead-exposure-a-review-c1ugct7w4r.pdf

Neurotoxic effects and biomarkers of lead exposure: a review.

https://b-neuro.com/pdfs/Neill-review.pdf

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: focus on NMDA receptor antagonism.

Neuroprotective activity of honokiol and magnolol in cerebellar granule cell damage.

Effects of honokiol and magnolol on acute and inflammatory pain models in mice.

Plasma membranes of animal cells are generally impermeable to macromolecules. Protein transduction mediated by protein transduction domains (PTDs) covalently cross-linked to cargoes for cellular internalization has previously been demonstrated. Peptides with PTDs could be an effective way to deliver proteins into living cells or tissues in vitro. In this report, we demonstrate that arginine-rich intracellular delivery (AID) peptides are able to facilitate the delivery of proteins into animal cells and to penetrate skin tissues rapidly. This cellular internalization and transdermal delivery of proteins is mediated by non-toxic AID peptides in a non-fusion protein and non-conjugation dependent manner. The efficiency of intracellular transport is further increased in the presence of chemical enhancer oleic acid. The mechanism of the AID-mediated cellular entry may involve macropinocytosis and actin rearrangement. Thus, we confirm that direct delivery of bioactive proteins into living cells and tissues mediated by non-covalent actions of AID peptides represents a useful strategy in pharmaceutics, therapeutics and cosmetics.

Transdermal delivery of proteins mediated by non-covalently associated arginine-rich intracellular delivery peptides.

Arginine-rich intracellular delivery peptides noncovalently transport protein into living cells.

Recent studies have shown that metabotropic glutamate receptor 5 (mGluR5) can modulate N-methyl-D-aspartate receptor function. Our previous findings demonstrated that the selective mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) and the antagonist 2-methyl-6-(phenylethynyl)-pyridine can reduce and enhance the ketamine anesthesia, respectively. The purpose of this study was to examine whether CHPG and positive allosteric modulator 3,3′-difluorobenzaldazine (DFB) can reverse ketamine-induced behavioral responses including locomotor hyperactivity, motor incoordination, sensorimotor gating deficit, and learning impairment. Mice were pretreated with CHPG (5–50 nmol,) or DFB (40–100 nmol) followed by ketamine administration. Locomotor activity, rotarod test, prepulse inhibition (PPI) of acoustic startle test, and novel object recognition test were examined. CHPG and DFB had no effect on these behaviors when administered alone. Both of them attenuated the locomotor hyperactivity, motor incoordination, and cognitive impairment induced by ketamine. However, the ketamine-induced PPI deficit was reversed by CHPG (50 nmol) but not by DFB (up to 100 nmol). CHPG and DFB have distinct potency and efficacy in attenuating ketamine-induced behavioral response. These behavioral data extend previous findings and further suggest that positive modulation of mGluR5 may provide a novel approach for development of antipsychotic agents.

Hwei-Hsien Chen

Papers

Neuroprotective activity of honokiol and magnolol in cerebellar granule cell damage.

Effects of honokiol and magnolol on acute and inflammatory pain models in mice.

Transdermal delivery of proteins mediated by non-covalently associated arginine-rich intracellular delivery peptides.

Arginine-rich intracellular delivery peptides noncovalently transport protein into living cells.

Attenuation of ketamine-evoked behavioral responses by mGluR5 positive modulators in mice