Characterisation and validation of novel, stable apelin-13 analogues on neurodegeneration in AD.

Introduction: Alzheimer’s disease is characterised by the cognitive decline, neuronal loss linked to oxidative stress, neuroinflammation, autophagy and endoplasmic reticulum (ER) stress. There are number of factors involved like lifestyle, genetics, age, and environment. After decades of research there is still no cure for Alzheimer’s. This thesis investigates the neuroprotective role of novel stable peptide apelin-13 analogues on cell survival and cell growth against various stressors induced in SH-SY5Y cells in-vitro.
Methods and results: SH-SY5Y neuronal cells were cultured and treated with the apelin-13 analogues in presence or absence of stressors under controlled condition to evaluate the effects on cell stress response and cell survival pathways. The cells were differentiated with retinoic acid to look at the cell proliferation and neurite extension. The treatments with apelin-13 analogues enhanced the cell viability , proliferation, modulated the oxidative stress and ER markers and promoted neurite outgrowth and differentiation. Furthermore, apelin-13 analogues reduced the pro-apoptotic and ER stress markers and led to increase in autophagy related proteins. The mechanistic study by AMPK knockdown showed that apelin-13 is AMPK dependant.
Conclusion: The result demonstrated that apelin-13 analogues protect against the neurotoxicity and oxidative stress by improving cell viability, proliferation and reducing cell toxicity. The apelin-13 analogues restored the autophagy and moderated the UPR activation via AMPK and PI3K/Akt pathway activation. Although further in-vivo studies are required to validate the results. This study provides new insight to the role of apelin-13 analogues as a therapeutic agent and pave a way for novel intervention targeting neurodegeneration.