Intercellular Communication and Vesicle-Mediated Pathology Propagation in Neurodegeneration

The central nervous system (CNS) is governed by complex intercellular communication networks that extend beyond traditional synaptic signaling. Soluble factors, direct membrane contacts, and extracellular vesicles (EVs) all mediate the exchange of information between diverse cell types. EVs transfer proteins, lipids, and nucleic acids between neurons, glia, and vascular-associated cells, orchestrating dynamic communication within the CNS. Increasing evidence highlights the role of EVs in the propagation of neurodegenerative pathology. In Alzheimer’s disease, EVs transport tau species between neurons and glial cells, potentially facilitating disease spread. In Parkinson’s disease and related synucleinopathies, vesicle-associated alpha-synuclein is believed to drive the intercellular propagation of misfolded proteins. EVs are also implicated in immune responses, tissue repair, and metabolic adaptation, while their cargo mirrors the physiological state of their cells of origin, presenting valuable opportunities as biomarkers. Importantly, EV-mediated signaling extends to the retina, where communication among Müller glia, retinal pigment epithelium, neurons, and vascular cells contributes to the progression of degenerative retinal diseases and opens avenues for diagnostics and therapy.This Research Topic aims to define the roles of extracellular vesicles as mediators of intercellular communication networks and as players in the propagation of pathology in neurodegenerative and retinal degenerative diseases. Our objective is to deepen mechanistic and causal understanding of how EVs coordinate neuron–glia and neurovascular interactions under both physiological and pathological conditions, dissect the pathways responsible for vesicle-mediated transfer of disease-associated proteins such as tau and alpha-synuclein, and clarify the contribution of glial EVs to neuroinflammation. In addition, we encourage exploration of EV signaling in retinal disease, and investigations into the use of EVs as biomarkers or engineered vehicles for therapeutic delivery where these approaches provide insight into underlying disease mechanisms.We welcome original research, reviews, and perspectives that address, but are not limited to, the following areas:- Mechanisms of EV biogenesis, cargo selection, and uptake in neurons, glia, or vascular-associated cells- Vesicle-mediated transfer and network-level propagation of tau, alpha-synuclein, and other neurodegenerative disease-associated molecules- Functional roles of glial EV signaling in neuroinflammation and disease modulation- Lipidomic, proteomic, and multi-omic profiling of EVs in the context of disease propagation in the CNS and retina, with clear links to underlying molecular or cellular mechanisms- The use of EVs as biomarkers, with emphasis on mechanistic insight into disease progression- Studies of EV roles in retinal degenerative conditions, highlighting unique cell–cell interactions- Strategies for engineering EVs for use as therapeutic delivery vehicles in neurodegenerative and retinal diseases supported by mechanistic evidence of actionWe especially encourage interdisciplinary and in vivo and disease-relevant preclinical studies that advance understanding of the mechanistic basis for EV-mediated pathology propagation and communication network modulation in neurodegeneration, including studies using animal models or patient-derived systems that provide insight into molecular and cellular disease mechanisms.Submissions should go beyond descriptive analyses and aim to provide mechanistic insight into how extracellular vesicles influence neurodegenerative processes. Studies that do not directly address neurodegenerative disease mechanisms or rely solely on simplified cell models without disease relevance may be considered out of scope. Topic editors: María Miranda, Inma Almansa Source: https://www.frontiersin.org/research-topics/79461/intercellular-communication-and-vesicle-mediated-pathology-propagation-in-neurodegeneration