Alzheimer's disease: Current concept and a new hope with siRNA-liposomal system

Abstract

Alzheimer's disease (AD) is a brain disorder that causes dementia and affects millions of people worldwide. Currently, the most effective pharmacological treatments for AD focus on alleviating and temporarily reducing symptoms rather than addressing the underlying mechanisms or achieving a complete cure. Advances in investigating the responsible genes and non-coding sequences at the molecular level of AD pathophysiology have led to numerous studies exploring small interfering RNA (siRNA)-based treatment. However, many challenges hinder the translation of siRNA into clinical trials, such as their in vivo poor stability and low cellular availability due to the presence of the blood-brain barrier (BBB). One strategy to bypass these limitations is the entrapment of siRNA within a liposomal system. Liposomes (LPs) are the most often utilized lipid-based nanovehicles due to their safe profile and ability to overcome the BBB through several mechanisms such as endocytosis, fusion, lipid exchange, and paracellular transport. This work aims to highlight the use of siRNA-loaded liposomal systems in targeting AD. It explores AD's pathophysiology and causes, the benefits of siRNA in treating this neurological disorder, and how LPs can advance this strategy and address current challenges.