RESUMO
Neuroprotective peptides are promising candidate molecules for the treatment of Alzheimer's disease (AD). Oral application of KED (Lys-Glu-Asp) improved memory and attention in elderly individuals with functional CNS disorders. Peptide KED also restores synaptic plasticity in in vitro model of AD. This review is focused on the analysis of the influence of KED peptide on the expression of genes and synthesis of proteins regulating apoptosis, aging, neurogenesis, and involved in AD pathogenesis. Analysis of published reports and our experimental findings suggests that KED regulates the expression of genes of cell aging and apoptosis (Ñ16, Ñ21), genes (NES, GAP43) and proteins (nestin, GAP43) of the neuronal differentiation, and genes involved in AD pathogenesis (SUMO, APOE, and IGF1). The study the effectiveness of neuroprotective peptide KED in animal models of AD seems to be very important.
Assuntos
Doença de Alzheimer , Neurogênese , Oligopeptídeos/farmacologia , Idoso , Envelhecimento/efeitos dos fármacos , Envelhecimento/genética , Envelhecimento/psicologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Animais , Senescência Celular/efeitos dos fármacos , Senescência Celular/genética , Modelos Animais de Doenças , Humanos , Neurogênese/efeitos dos fármacos , Neurogênese/genética , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/genética , Oligopeptídeos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
Molecular mechanisms of the neuroprotective effect of peptide T-33 and cortexin were studied on organotypic cultures of the brain from young and old Wistar rats. The effective concentration of peptide T-33 stimulating proliferative activity of neurons considerably surpassed that of cortexin. Cortexin and peptide T-33 stimulated the expression of serotonin, Ki-67, and vimentin in cells of the brain cortex; peptide T-33 was most effective in this respect.
Assuntos
Envelhecimento/metabolismo , Peptídeos/metabolismo , Animais , Ratos , Ratos WistarRESUMO
Peptides Glu-Asp-Arg and Lys-Glu-Asp stimulate serotonin expression in aging cultures of brain cortex cells. Peptide regulation of 5-tryptophan hydroxylase gene encoding the enzyme involved in serotonin synthesis was demonstrated by the molecular docking method. The CCTGCC nucleotide sequence in 5-tryptophan hydroxylase gene was found to be complementary to these peptides. Hence, Glu-Asp-Arg and Lys-Glu-Asp peptides epigenetically regulate serotonin synthesis in the brain cortex, which indicates their neuro- and geroprotective activities.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Oligopeptídeos/farmacologia , Serotoninérgicos/farmacologia , Serotonina/biossíntese , Animais , Sequência de Bases , Sítios de Ligação , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Simulação de Acoplamento Molecular , Dados de Sequência Molecular , Cultura Primária de Células , Ligação Proteica , Ratos , Ratos Wistar , Serotonina/genética , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismoRESUMO
We studied the effect of 20 standard L-amino acids on proliferation of the nervous, cardiovascular, urogenital, digestive, and immune system tissues from young and old animals in organotypic cultures. The effect of amino acids on tissue culture proliferation depended on their origin and animal age.
Assuntos
Aminoácidos/fisiologia , Envelhecimento , Animais , Encéfalo/citologia , Proliferação de Células , Masculino , Miocárdio/citologia , Especificidade de Órgãos , Ratos Wistar , Regeneração , Baço/citologia , Técnicas de Cultura de TecidosRESUMO
The review presents comparative characteristics of 2 peptide neuroprotective groups: polypeptide complexes (cortexin, cerebrolizin) and short peptides (semax, kortagen, pinealon). The data of clinical applying of peptides in elderly and old age people and cellular and molecular mechanisms of their neuroprotective activity is described.
