epidermal-growth-factor and Memory-Disorders

Recent studies have proposed that microRNAs (miR) function as novel diagnostic and prognostic biomarkers and therapeutic targets in Alzheimer's disease (AD), a common disease among the elderly. In the current study, we aim to explore the effect of miR-186 on oxidative stress injury of neuron in rat models of AD with the involvement of the interleukin-2 (IL2) and the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathways. AD rat models were established, and dual-luciferase reporter assay and online software were used to confirm the targeting relationship between miR-186 and IL2. Immunohistochemistry was used evaluating the positive rate of IL2. Afterward, to define the role of miR-186 in AD, miR-186, IL2, and JAK-STAT related protein (JAK2, STAT3) expressions were quantified. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide, and cell apoptosis was detected by flow cytometry. We observed downregulated miR-186 and IL2 and upregulated JAK-STAT signaling pathway related genes in AD. The overexpression of miR-186 was shown to significantly promote cell proliferation while suppressing cell apoptosis along with the expression of the IL2 and JAK-STAT signaling pathway related protein. Collectively, the key findings obtained from the current study define the potential role of miR-186 as an inhibitor of AD development by downregulation of IL2 through suppression of the JAK-STAT signaling pathway.

Topics: Alzheimer Disease; Animals; Apoptosis; Base Sequence; bcl-2-Associated X Protein; Caspase 3; Disease Models, Animal; Down-Regulation; Epidermal Growth Factor; Glutathione Peroxidase; Growth Hormone; Hippocampus; Interferon-gamma; Interleukin-2; Janus Kinases; L-Lactate Dehydrogenase; Male; Malondialdehyde; Memory Disorders; MicroRNAs; Neurons; Oxidative Stress; Platelet-Derived Growth Factor; Rats, Sprague-Dawley; Reaction Time; Reactive Oxygen Species; STAT3 Transcription Factor; Superoxide Dismutase

A group of growth factors have been shown to play important roles in amelioration of the malfunction of the neurodegenerative diseases. However, the proteins or polypeptides passing across the blood-brain barrier (BBB) to access the brain parenchyma are relatively few so that it hinders the therapies in clinic. Here a genetically reconstructed fusion peptide of human epidermal growth factor (hEGF) with an undecapeptide YGRKKRRQRRR (P11) was used to investigate the permeability between the cell membrane and the BBB via rectal administration. The efficiency to rescue the Aβ 22-35-induced dementia in mice was assessed after administration of P11-hEGF per rectal. Our results showed that P11-hEGF permeates across not only the 3T3 cell membrane in vitro, but also the endothelia of vessels after intravenous injection (IV), and the mucosa of the rectum after per rectal administration. Further results showed that the circulating P11-hEGF allowed penetrating through the blood-brain barrier and then getting into the brain manifesting biological responses. In the animal experiments, treatment with P11-hEGF not only ameliorated the dementia induced by Aβ 22-35 but also rescued the dementia of the aged mice, no matter how it was administrated (IV or per rectal). These results suggest that the rectal non-invasive delivery of the P11 polypeptide-conjugated growth factor is an efficient way for BBB transduction, thus raises the hope of real therapeutic progress against neurodegenerative diseases.

Topics: Administration, Rectal; Amyloid beta-Peptides; Animals; Blood-Brain Barrier; Brain; Cell Membrane Permeability; Cell Proliferation; Dementia; Epidermal Growth Factor; Humans; Learning Disabilities; Memory Disorders; Mice; Oligopeptides; Recombinant Fusion Proteins