The effect of a neuroprotective dose of isatin or deprenyl to mice on the profile of brain isatin-binding proteins

Abstract

Isatin (indol-2,3-dione), an endogenous biofactor found in the brain, peripheral tissues and biological body fluids of humans and animals, exhibits a wide range of biological and pharmacological activities. They are realized via interaction with numerous isatin-binding proteins. Some of these proteins identified during proteomic profiling of the brain are involved in the development of neurodegenerative pathology. In the context of the neuroprotective effect, the effect of isatin is comparable to the effects of deprenyl (selegiline), a pharmacological agent used for treatment of Parkinson's disease. In this study, we have investigated the effect of a single dose administration of isatin (100 mg/kg) and deprenyl (10 mg/kg) to mice on the profile of the brain isatin-binding proteins. Comparative proteomic analysis of brain isatin-binding proteins of mice treated with isatin or deprenyl resulted in identification of a representative group of proteins (n=200) sensitive to the administration of these substances. The change in the profile of isatin-binding proteins may be obviously attributed to accumulation of isatin and deprenyl in the brain and their interaction with target proteins; this prevents protein binding to the affinity sorbent. Thus identified brain isatin-binding proteins of the control animals obviously represent specific targets that interact directly with isatin (and also with deprenyl) in vivo. Isatin or deprenyl administered to animals interact with these proteins and thus inhibit their binding to the affinity sorbent (immobilized isatin analogue).

A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research

“…It should be noted that after administration of the neuroprotective doses of isatin (50-100 mg/kg), its concentration in the brain may exceed 70 µM [1,4]. Our recent study has shown that treatment of mice with a neuroprotective dose of isatin significantly influenced the proteomic profile of brain isatin-binding proteins [48]. The detected changes in the profile of isatin-binding proteins are consistent with the accumulation of administered isatin in the brain and its binding to target proteins, thus preventing subsequent protein binding to the affinity sorbent containing an isatin analogue as the affinity ligand [48].…”

“…Our recent study has shown that treatment of mice with a neuroprotective dose of isatin significantly influenced the proteomic profile of brain isatin-binding proteins [48]. The detected changes in the profile of isatin-binding proteins are consistent with the accumulation of administered isatin in the brain and its binding to target proteins, thus preventing subsequent protein binding to the affinity sorbent containing an isatin analogue as the affinity ligand [48]. Earlier, we also demonstrated that within a slightly different scheme of the animal experiment, pretreatment of rats with a neuroprotector dose of isatin prevented brain MAO B against irreversible inhibition by the mechanism-based inhibitor phenelzine [49].…”

Tryptophan Metabolites as Mediators of Microbiota-Gut-Brain Communication: Focus on Isatin

“…Isatin interacts with numerous isatin-binding proteins, which have been identified during affinity-based proteomic profiling of mouse and rat brain tissue lysates (Buneeva et al, 2010(Buneeva et al, , 2012(Buneeva et al, , 2019Medvedev et al, 2020). proteins/enzymes; and (VI) Metabolism of amino acids and other nitrogenous compounds.…”

Isatina, un compuesto endógeno a considerar en la Enfermedad de Parkinson

“…Además, en cultivos celulares la isatina presenta efectos protectores en neuronas dopaminérgicas y también se describe neuroprotección en el modelo de ratón de EP inducido por la neurotoxina 1-metil-4-fenil-1, 2, 3, 6tetrahidropiridina (MPTP) (8). Como agente neuroprotector, la isatina actúa sobre la gliceraldehído-3-fosfato deshidrogenasa (GAPDH), considerada posible diana terapéutica en patologías como la demencia senil, la epilepsia y la EP (9). El perfil proteómico de la isatina revela que este compuesto presenta capacidad para unirse a 200 proteínas cerebrales en ratones, mostrando un comportamiento análogo al de la selegilina (9).…”

“…Como agente neuroprotector, la isatina actúa sobre la gliceraldehído-3-fosfato deshidrogenasa (GAPDH), considerada posible diana terapéutica en patologías como la demencia senil, la epilepsia y la EP (9). El perfil proteómico de la isatina revela que este compuesto presenta capacidad para unirse a 200 proteínas cerebrales en ratones, mostrando un comportamiento análogo al de la selegilina (9). Esto abre la puerta a plantear que, al igual que la selegilina, el posible efecto neuroprotector de la isatina podría ser independiente a la inhibición de la MAO-B.…”