The Role of Exosomes as Mediators of Neuroinflammation in the Pathogenesis and Treatment of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a common neurodegenerative disease characterized by progressive dementia. Accumulation of β–amyloid peptide 1–42 and phosphorylation of tau protein in the brain are the two main pathological features of AD. However, comprehensive studies have shown that neuroinflammation also plays a crucial role in the pathogenesis of AD. Neuroinflammation is associated with neuronal death and abnormal protein aggregation and promotes the pathological process of β-amyloid peptide 1–42 and tau protein. The inflammatory components associated with AD include glial cells, complement system, cytokines and chemokines. In recent years, some researchers have focused on exosomes, a type of membrane nano vesicles. Exosomes can transport proteins, lipids, microRNAs and other signaling molecules to participate in a variety of signaling pathways for signal transmission or immune response, affecting the activity of target cells and participating in important pathophysiological processes. Therefore, exosomes play an essential role in intercellular communication and may mediate neuroinflammation to promote the development of AD. This paper reviews the occurrence and development of neuroinflammation and exosomes in AD, providing a deeper understanding of the pathogenesis of AD. Furthermore, the role of exosomes in the pathogenesis and treatment of AD is further described, demonstrating their potential as therapeutic targets for neuroinflammation and AD in the future.

Integrin β3-Mediated Cell Senescence Associates with Gut Inflammation and Intestinal Degeneration in Models of Alzheimer’s Disease

“…In the 9 month 5XFAD colon tissue dataset, vesicle-mediated transport ( p = 8.53*10 −13 ) and lipid metabolic processes ( p = 9.82*10 −12 ) were the top two enriched pathways ( Figure 2 D). Immune responses, vesicle transportation, and lipid metabolism mutually affect each other in AD [ 39 , 40 , 41 ]. This cross-sectional proteomic analysis suggested that 5XFAD mouse colonic tissue underwent time-sensitive and complex proteomic alterations during AD development, with striking shifts away from early immune response signatures at 3 and 6 months to dysregulated lipid metabolism at 9 months ( Figure 2 D).…”

Bibliometric analysis of research on Alzheimer’s disease and non-coding RNAs: Opportunities and challenges

“…And revealing the regulatory mechanism of ncRNAs in AD from the perspective of neuroinflammation can provide new ideas for the treatment of AD ( Lan et al, 2021 ; Zingale et al, 2021 ). A recent review article also shows that ncRNAs in exosomes can mediate nerve inflammation and promote the development of AD ( Weng et al, 2022 ). In addition, memory deficits are the main characteristics of AD, and improving memory deficits by regulating ncRNAs is also a future research direction ( Ju et al, 2021 ; Xiao et al, 2021 ; Zhang G. J. et al, 2022 ).…”

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

“…Various types of inflammasomes are also present in the cytosol of microglia, astrocytes, and neurons, where their activation contributes to the development and progression of neurodegenerative diseases in which inflammation is considered a common pathophysiological mechanism [ 1 , 247 , 248 ]. Neuroinflammation may involve exosomes that transport Aβ, tau, inflammatory factors, and other pathogenic substances between microglia, astrocytes, and neurons [ 249 , 250 ]. Exosome-inflammasome crosstalk has been documented: inflammasome activation can regulate exosomes release, and exosomes are an upstream regulator for inflammasome activation or inhibition [ 251 ].…”