Exosomes and non-coding RNAs: bridging the gap in Alzheimer's pathogenesis and therapeutics

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• Alzheimer's disease (AD) is the primary cause of dementia in the elderly, linked to neurodegeneration and impaired waste clearance.
• The vascular hypothesis posits early vascular damage contributes to AD pathogenesis, including amyloid plaque and Tau tangle accumulation.
• Non-coding RNAs (ncRNAs), such as long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are implicated in AD regulation.

Purpose of the Study:

• To review the multifactorial nature of Alzheimer's disease.
• To explore the regulatory roles of ncRNAs in AD pathogenesis.
• To discuss the potential of exosome-mediated delivery of ncRNAs for AD treatment.

Main Methods:

• Literature review of studies on Alzheimer's disease, ncRNAs, and exosomes.
• Analysis of the complex regulatory networks involving ncRNAs as competitive endogenous RNAs.
• Examination of exosome function in intercellular ncRNA transfer across the blood-brain barrier.

Main Results:

• ncRNAs are involved in regulating multiple pathogenic mechanisms of AD.
• lncRNAs and circRNAs can act as competing endogenous RNAs, inhibiting miRNAs and forming regulatory networks.
• Exosomes can transfer ncRNAs between cells, potentially crossing the blood-brain barrier and offering a non-immunogenic drug delivery strategy.

Conclusions:

• Alzheimer's disease is a complex neurological disorder with multifactorial origins.
• ncRNAs offer a promising avenue for understanding and targeting multiple AD pathogenic pathways.
• Exosome-based delivery of ncRNAs presents a potential therapeutic strategy for central nervous system diseases like AD.