The role of GLP-1/GIP receptor agonists in Alzheimer's disease.

BACKGROUND: New glucagon-like peptide-1 (GLP-1) analogues developed in recent years have a long half-life and offer further prospects for clinical application. At present, the neuroprotection of GLP-1 analogues in Alzheimer's disease (AD) has just begun to be explored. OBJECTIVES: To investigate how glucagon-like peptide-1 (liraglutide) plays a protective role in AD by regulating tau activation and BACE1 expression. MATERIAL AND METHODS: Human neuroblastoma cell line SH-SY5Y cells were cultured in vitro and pretreated with different concentrations of liraglutide, and then treated with different concentrations of okadaic acid (OA) in order to observe the apoptosis of the SH-SY5Y cells. After liraglutide treatment, the apoptosis of neurons in AD rats was detected using flow cytometry, and tau activation and ß-site APP cleaving enzyme 1 (BACE1) expression were detected using western blot. RESULTS: Different concentrations of OA were able to induce apoptosis of SH-SY5Y cells in a dose-dependent manner. Different concentrations of liraglutide were used to pretreat SH-SY5Y cells, which were able to protect the SH-SY5Y cells from apoptosis induced by OA. Okadaic acid significantly increased tau activation and BACE1 expression in the SH-SY5Y cells, which was blocked with liraglutide pretreatment. The results of a water maze experiment showed that liraglutide had significant protective effects on memory and cognitive ability in AD rats induced with OA, inhibited apoptosis of neural cells in AD rats, and inhibited tau activation and BACE1 expression of neural cells in AD rats induced with OA. CONCLUSIONS: Liraglutide has a protective effect on AD in vivo and in vitro, which may be mediated by preventing neuronal apoptosis and inhibiting the activation of tau and the expression of BACE1.

The clinical assessment of amyotrophic lateral sclerosis patients' prognosis by ZNF512B gene, neck flexor muscle power score and body mass index (BMI).

BACKGROUND: Assessment on the prognosis of amyotrophic lateral sclerosis (ALS) is becoming a focus of research in recent years since there is no effective treatment. The aim of the research is to explore the major factors involving in prognosis of ALS patients through long-term follow-up. METHODS: ALS patients' DNA extracted from peripheral blood white cells were detected for the risk allele by single nucleotide polymorphism (SNP) analysis. Neck flexor muscle score and body mass index (BMI) were recorded during Medical Research Council follow-up using manual muscle testing method. RESULTS: ALS patients with risk alleles (C) deteriorated rapidly with poor clinical outcome. It seemed that the higher neck flexor muscle strength score in ALS patients with the longer survival time but without significant correlation (p > 0.05). The lower the basal body mass index, the shorter the survival time and the faster deterioration (p < 0.05). The patients with body mass index less than 22.04 seemed to have short survival time than those with BMI more than 22.04 (p < 0.05), however, the speed of deterioration in two groups of patients had no significant difference (p > 0.05). CONCLUSION: The risk (C) allele of the SNP (rs2275294) in the ZNF512B gene, cervical flexor muscle power and body weight index might have clinical potential for ALS prognostication, since these indicators is so simple to perform that they might be very suitable for primary clinics and even community medical institutions to carry out.