Protective Effect of Trehalose Sugar on Amyloid-Membrane Interactions using BLM Electrophysiology

Abstract: Alzheimer's disease (AD) is a neurodegenerative disease characterized by dementia and memory loss in the elderly population. The amyloid-$\beta$ peptide (A$\beta$ 1-42) is one of the main pathogenic factors in AD and is known to cause damage to neuronal cellular membranes. There is no cure currently available for AD and new approaches, including preventive strategies, are highly desirable. In this work, we explore the possibility of protecting neuronal membranes from amyloid-induced damage with naturally existing sugar trehalose. Trehalose has been shown to protect plant cellular membranes in extreme conditions and modify A$\beta$ misfolding. We hypothesize that trehalose can protect the neuronal membrane from amyloid toxicity. In this work, we studied the protective effect of trehalose against A$\beta$-induced damage in model lipid membranes (DPPC/POPC/Cholesterol) to mimic neuronal membranes using atomic force microscopy (AFM) and black lipid membrane (BLM) electrophysiology. Our results demonstrated that A$\beta$1-42 damaged membranes and led to ionic current leakage across these membranes due to the formation of various defects and pores. The presence of trehalose reduced the ion current across membranes caused by A$\beta$1-42 peptide damage, thus efficiently protecting the membranes. These findings suggest the trehalose sugar can be useful in protecting neuronal cellular membranes against amyloid toxicity in AD prevention.