Epigenetic Alterations in Alzheimer's Disease: Impact on Insulin Signaling and Advanced Drug Delivery Systems.

Simple Summary: This review mainly focuses on epigenetic changes in a few selective genes associated with insulin insensitivity in the periphery and how this peripheral insulin insensitivity is linked with impaired signaling of insulin in the brain, thus causing Alzheimer's disease. DNA methylation and histone modifications are the focus of this review, with primary importance given to DNA methylation. Moreover, there has been a focus shift from the amyloid β hypothesis to epigenetic mechanisms. Furthermore, we discuss the advanced drug delivery systems that can be used for the delivery of drugs targeting the brain during Alzheimer's disease. The advanced drug delivery systems discussed in this paper are nanoparticles, vesicular systems, network systems and dendrimers, hydrogel-based systems, and biologics. Alzheimer's disease (AD) is a neurodegenerative condition that predominantly affects the hippocampus and the entorhinal complex, leading to memory lapse and cognitive impairment. This can have a negative impact on an individual's behavior, speech, and ability to navigate their surroundings. AD is one of the principal causes of dementia. One of the most accepted theories in AD, the amyloid β (Aβ) hypothesis, assumes that the buildup of the peptide Aβ is the root cause of AD. Impaired insulin signaling in the periphery and central nervous system has been considered to have an effect on the pathophysiology of AD. Further, researchers have shifted their focus to epigenetic mechanisms that are responsible for dysregulating major biochemical pathways and intracellular signaling processes responsible for directly or indirectly causing AD. The prime epigenetic mechanisms encompass DNA methylation, histone modifications, and non-coding RNA, and are majorly responsible for impairing insulin signaling both centrally and peripherally, thus leading to AD. In this review, we provide insights into the major epigenetic mechanisms involved in causing AD, such as DNA methylation and histone deacetylation. We decipher how the mechanisms alter peripheral insulin signaling and brain insulin signaling, leading to AD pathophysiology. In addition, this review also discusses the need for newer drug delivery systems for the targeted delivery of epigenetic drugs and explores targeted drug delivery systems such as nanoparticles, vesicular systems, networks, and other nano formulations in AD. Further, this review also sheds light on the future approaches used for epigenetic drug delivery. [ABSTRACT FROM AUTHOR]