Exploration of Neuroprotective Therapy

Table 1. Mechanisms of exosome-mediated neuroprotection and regeneration.

Mechanistic category	Molecular mediators	Primary target/effect	Downstream signaling pathway	Functional outcome
Anti-apoptotic	miR-21, miR-124, Bcl-2	Inhibits PTEN, PDCD4	PI3K/Akt, MAPK/ERK	↑ Cell survival, ↓ caspase activity
Antioxidant	miR-199a-5p, HO-1, NQO1	Stabilizes Nrf2	Nrf2/HO-1 signaling	↓ ROS, ↓ lipid peroxidation
Synaptic plasticity	miR-124, miR-9	Remodels dendritic spines	Rho-GTPase modulation	↑ Synaptogenesis, ↑ LTP
Angiogenesis	miR-125a, VEGF	Endothelial proliferation	PI3K/Akt and ERK	↑ Cerebral perfusion
Axonal regeneration	miR-133b, GAP-43	Promotes axonal sprouting	ERK/CREB, STAT3	↑ Motor recovery
Immunomodulation	miR-146a, miR-124	Microglial M1 → M2 shift	NF-κB inhibition	↓ TNF-α, ↓ IL-6, ↓ IL-1β
BBB integrity	MCP-1, VEGF, miR-21	Enhances astrocyte function	PI3K/Akt	↓ BBB leakage, ↑ tight junctions

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Akt: protein kinase B; BBB: blood-brain barrier; ERK: extracellular signal-regulated kinase; IL: interleukin; miRNA: microRNA; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; Nrf2: nuclear factor erythroid 2-related factor 2; PI3K: phosphoinositide 3-kinase; ROS: reactive oxygen species; STAT3: signal transducer and activator of transcription 3; TNF: tumor necrosis factor; VEGF: vascular endothelial growth factor; LTP: long-term potentiation; MAPK: mitogen-activated protein kinase.

Declarations

Author contributions

AWI: Conceptualization, Supervision, Writing—original draft, Writing—review & editing. ZKR: Conceptualization, Writing—original draft, Writing—review & editing. HSW: Writing—original draft, Writing—review & editing, Supervision. BS: Writing—original draft, Writing—review & editing. SH: Writing—original draft, Writing—review & editing. SRK: Writing—review & editing. All authors read and approved the submitted version.

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The authors declare that they have no conflicts of interest.

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