EVs in neurological disorders: pathogenic mechanisms and therapeutic applications.
| Disease | Pathogenic EV cargo | Disease propagation mechanism | Therapeutic EV applications | Biomarker potential | Key citations |
|---|---|---|---|---|---|
| Alzheimer’s disease | Aβ peptides, phosphorylated tau (pT181), and truncated tau filaments | Intercellular spread of protein aggregates, tau seeding, and neurofibrillary tangle formation | MSC-derived EVs for neuroprotection, miRNA delivery for cognitive enhancement | Plasma EV tau and Aβ42 correlate with CSF biomarkers and cognitive decline | [73–76, 95] |
| Parkinson’s disease | α-synuclein (oligomeric and phosphorylated forms), LRRK2, pT73-Rab10 | Prion-like spreading of α-synuclein, microglial activation, and neuroinflammation | Catalase-loaded EVs for dopaminergic neuroprotection, anti-inflammatory EV therapy | Urinary EV proteomic profiles achieve 76–86% diagnostic accuracy | [89, 92, 104] |
| Amyotrophic lateral sclerosis | TDP-43 (full-length and C-terminal fragments), mutant SOD1 | Intercellular toxicity transfer, protein aggregation induction, and motor neuron degeneration | Engineered EVs for neuroprotective factor delivery, RNA therapeutics | EV-mediated TDP-43 correlates with disease severity and progression | [93–95] |
| Multiple sclerosis | Pro-inflammatory cytokines, matrix metalloproteinases, and inflammatory miRNAs | BBB disruption, demyelination promotion, and immune cell activation | Immunomodulatory EVs, remyelination-promoting factors | CSF-derived EVs show unique protein enrichment profiles for disease monitoring | [96, 97, 105] |
| Stroke | Inflammatory miRNAs, tight junction disruptors, pro-inflammatory mediators | BBB permeability increase, endothelial dysfunction, and edema exacerbation | miR-124 and miR-181b delivery for neurogenesis and angiogenesis, neuroprotective EVs | Brain-derived EVs reflect acute injury status and recovery potential | [106, 107] |
Aβ: amyloid-β; BBB: blood-brain barrier; CSF: cerebrospinal fluid; EVs: extracellular vesicles; LRRK2: leucine-rich repeat kinase 2; miRNAs: microRNAs; MSC: mesenchymal stem cell; SOD1: superoxide dismutase 1; TDP-43: TAR DNA-binding protein 43.
MAM: Writing—original draft, Writing—review & editing, Visualization. MMH: Conceptualization, Writing—original draft, Writing—review & editing, Visualization. Both authors read and approved the submitted version.
The authors declare that they have no conflicts of interest.
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