RESUMO
Huntington's disease is a hereditary neurodegenerative disease that primarily affects striatal neurons. Recent studies demonstrated abnormalities in calcium regulation in striatal neurons in Huntington's disease, which leads to elimination of synaptic connections between cortical and striatal neurons. In the present study, we focused on the neuroprotective properties of σ1-receptor, because one of its main functions is associated with modulation of calcium homeostasis in cells. The application of selective σ1-receptor agonists to the corticostriatal cell culture restores synaptic connections between the cortical and striatal neurons. Based on the obtained data, we assume that σ1-receptor is a promising target for the development of drugs for the therapy of Huntington's disease.
Assuntos
Cálcio/metabolismo , Doença de Huntington/genética , Neurônios/metabolismo , Receptores sigma/genética , Transmissão Sináptica/genética , Animais , Anisóis/farmacologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Corpo Estriado/metabolismo , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/patologia , Expressão Gênica , Homeostase , Doença de Huntington/metabolismo , Doença de Huntington/patologia , Masculino , Camundongos , Modelos Biológicos , Morfolinas/farmacologia , Neurônios/patologia , Piperidinas/farmacologia , Cultura Primária de Células , Propilaminas/farmacologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores sigma/agonistas , Receptores sigma/antagonistas & inibidores , Receptores sigma/metabolismo , Sinapses/metabolismo , Sinapses/patologia , Transdução Genética , Receptor Sigma-1RESUMO
On the page 553 Acknowledgements should be as follows: The study was supported by the Russian Science Foundation (grant 14-25-00024-P).
RESUMO
In primary culture of mouse hippocampal neurons, peptide EDR (200 ng/ml) under conditions of amyloid synaptotoxicity (a model of Alzheimer's disease) increased the number of mushroom spines by 71% and returned this parameter to the normal level. Under the same conditions, tripeptide KED (200 ng/ml) increased the number of mushroom spines in hippocampal neurons by 20%. Tripeptide EDR can be recommended for further experimental study as a candidate neuroprotective agent for prevention and treatment of Alzheimer's disease.
Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Espinhas Dendríticas/metabolismo , Hipocampo/citologia , Neurônios/efeitos dos fármacos , Peptídeos/uso terapêutico , Animais , Células Cultivadas , Modelos Animais de Doenças , CamundongosRESUMO
The article discusses the pool of signaling molecules that regulate the functional activity of the skin cells. Molecules of apoptosis and cells skin aging are p53, p21, p15, Cdk 4/6 and Bcl-2. Inflammation in skin fibroblasts are realized through the cytokines TNF-α, TGF-ß, IL-1, ICAM-1, matrix metalloproteinase MMP-1,2,3,9, transcription factor NF-κB and activator protein AP-1. An important role in the aging of skin cells play neuroimmunoendocrine signaling molecules--melatonin, serotonin, skin fibroblast proliferation marker chromogranin A and CD98hc. Age-related changes in the activity of immune cells of the skin is associated with impaired expression of cluster of differentiation of T-lymphocytes (CD3, CD4, CD5, CD8, CD11) and dendritic cells (CD83âº). These signaling molecules produced by the fibroblasts of the skin, regulate the activity of immune cells involved in the cascade of reactions associated with inflammatory responses, proliferation, apoptosis and cell regeneration. Based on these data nowadays new highly selective approaches to the diagnosis of the skin and the creation of cosmetic agents for the prevention of aging are developed.
Assuntos
Envelhecimento/genética , Citocinas/genética , Inflamação/genética , Pele/metabolismo , Envelhecimento/patologia , Antígenos CD/biossíntese , Antígenos CD/genética , Apoptose/genética , Apoptose/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Citocinas/biossíntese , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Inflamação/fisiopatologia , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Pele/patologia , Pele/ultraestruturaRESUMO
The review covers the main functions of the family of adhesion molecules JAMs (Junctional adhesion molecules). This review provides information about the role of the molecules JAM-AH, JAM-BH and JAM-CF in the occurrence of pathological conditions, including diseases of the nervous and cardiovascular systems, atherosclerosis, thrombosis and malignant growth. A molecule JAM-C and JAM-C directly affect platelet's adhesion to endothelial and dendritic cells, neutrophils, and other types of leukocytes, which makes their involvement in the regulation of hemostasis, and migration processes. JAM-A has an effect on the inflammatory response, leading to impaired cognitive function in HIV infection. JAM-B is involved in suppression of tumor growth in patients with Down syndrome. It is described the role of molecule JAM-A and JAM-C in the pathogenesis of hypertension, hypertensive crisis, atherosclerosis, cardiac abnormalities in the syndrome of Jacobson. Molecules JAM-B and JAM-C reduce the growth and invasion of human gliomas, and JAM-A has static effect against breast cancer. JAM-A molecule, JAM-B and JAM-C are involved in the development of inflammatory reactions and pathological neoangiogenesis in the cornea. The molecule JAM-C is involved in differentiation and polarization photoreceptors of the retina. The review provides own data of the authors, suggests the presence of epigenetic mechanisms of regulation of expression of the family of molecules JAMs, carried out with the direct participation of peptide geroprotectors.