A1.a. Disease Mechanisms, Pathophysiology: Abeta aggregation, protein misfolding

P009 - PROTEOMIC ANALYSIS OF NEUROTROPHIC AND NEUROPROTECTIVE EFFECTS OF PREGNENOLONE SULFATE IN ALZHEIMER’S DISEASE

Presentation Topic
A1.a. Disease Mechanisms, Pathophysiology: Abeta aggregation, protein misfolding
MP3

Abstract

Aims

Background: Alzheimer’s disease (AD) is the most common cause of dementia in the elderly. The toxicity of b-amyloid (Ab) peptides is thought to be involved in neuronal damage and cognitive decline in this pathology. Multiple studies focused on role of neuroprotective molecules including Pregnenlone Sulfate (PREGS) to attenuate the toxic consequences of Ab peptides in the development of AD.

Aims: Our objective is to investigate the proteomic analysis of neurotrophic and neuroprotective effects of PREGS on in vitro model of AD.

Methods

Methods:

Proteins were extracted from neuroblastoma B104 cells pretreated either with PREGS alone or PREGS before Aβ25–35. Extracted proteins were subjected to proteomic analysis using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to generate expression proteomics data based on both qualitative and quantitative differential expression changes between the sample groups.

Results

Results:

The proteomic analysis revealed 260 significantly differentially expressed proteins (ANOVA test p< 0.05, >1.5-fold change (FC)) in 2 groups including Aβ25–35 treated cells compared to PREGS and Aβ25–35 treated ones (186 up and 74 down). As to control compared to PREGS treated cells, we found 38 significantly differentially expressed proteins (26 up and 12 down). Functional network analysis using ingenuity pathway analysis (IPA) revealed presence of AD related proteins such as NCAM1, CDC42, RAC1, RHOG, HSPA5, GNB2l1 and TPM1.

Conclusions

Conclusion:

Thus, PREGS is neuroprotective and neurotrophic drug that could be promising in Alzheimer’s disease treatment. The continuity in examining the mechanism(s) underlying PREGS activity is promising towards identifying efficient therapy for AD.

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