Modulation of autophagy has been shown to have therapeutic potential for Alzheimer’s disease through favouring the clearance of aggregate prone proteins such as amyloid-? and p-Tau. Recent research has shown that spermidine and rilmenidine have the potential to affect autophagy, but the exact relationship between autophagy, protein clearance and cell death remains unclear. Moreover, the impact of concentration differences on autophagic flux and on subsequent protein clearance and neuronal toxicity is uncertain. Therefore, we aimed to characterize the autophagic profile of rilmenidine and spermidine to assess the degree of protection and protein clearance in a paraquat induced neuronal toxicity model of Alzheimer’s disease.

 
We found that spermidine and rilmenidine modulate autophagic flux in a concentration dependent manner. Both these agents up-regulated autophagy, improved cell viability through clearance of protein aggregates and protected the cells against paraquat induced neuronal toxicity. In addition, spermidine protects against mitochondrial and tubulin network damage. These findings suggest that precision controlled induction of autophagy may be a suitable pharmacological target for preserving neuronal cell viability in Alzheimer’s disease. Future work is required to better quantify autophagic flux.

Stellenbosch University