Table 2.

Role of ADEVS in Neurological and Neurodegenerative Diseases

Neurological Disease/Model	Known or Potential Composition of ADEVs	Potential Adverse Effects mediated by ADEVs	References
Alzheimer’s disease	EVs enriched with Aβ42 protofibrils and ApoE ɛ4	Neurotoxicity of neighboring neurons, less effective clearing of Aβ42 peptides	[137–143]
Alzheimer’s disease	EVs enriched with BACE-1, sAPPβ, and various complement proteins	Neuroinflammatory cascade and neurodegeneration	[145, 147–148]
Stroke or ischemia	EVs enriched with SEMA3A	Activation of astrocytes, diminished axon growth, neurodegeneration	[154–157]
Parkinson’s Disease	EVs enriched with miR-34a following exposure to LPS	Increased dopaminergic neurodegeneration following exposure to a neurotoxin	[136]
Amyotrophic lateral sclerosis	EVs enriched with mutant SOD1	Increased oxidative stress, neuroinflammation, and death of motoneurons	[158]
Amyotrophic lateral sclerosis	EVs enriched with mutant TDP-43	Neurodegeneration	[1, 161–163]
Amyotrophic lateral sclerosis	EVs enriched with FUS	Juvenile-onset of ALS	[1, 161]
Amyotrophic lateral sclerosis	EVs enriched with DRPs	Neurodegeneration	[165]
Amyotrophic lateral sclerosis	EVs with depleted miR-49–3p	Upregulation of SEMA3A and neurodegeneration	[157]
Inflammatory Brain Injury using IL-1β injection	EVs containing unknown cargo	Inhibition of PPARα, secretion of cytokines in the liver and mobilization of peripheral immune cells to the brain	[166]
Opiate abuse (morphine induced prototype)	EVs enriched with lincRNA-Cox2	Impaired phagocytosis by microglia, activation of TLR-7 signaling pathway	[167–169]
HIV-associated brain dysfunction	EVs enriched with nef	Increased oxidative stress, reduced neurite growth, and cognitive impairment	[170–173]
HIV-associated brain dysfunction	EVs enriched with HIV-1 Tat	Reduced neurite growth, and neurodegeneration	[174]
miR-9	EVs enriched with miR-9	Enhanced microglial migration	[175]
Zika virus mediated brain dysfunction	EVs enriched with Zika viral particles	Neurodegeneration	[177]
Alcohol-induced brain dysfunction	EVs enriched with pro-inflammatory cytokines and miRs	Neuroinflammation and brain dysfunction	[178]

Abbreviations: Aβ42, amyloid-beta 42; ApoE ɛ4, apolipoprotein E allele 4; BACE-1, β-site amyloid precursor protein-cleaving enzyme 1; DRPs, dipeptide repeat proteins; FUS, fused in sarcoma; HIV, human immunodeficiency virus; IL-1β, interleukin-1 beta; lincRNA-Cox2, long intergenic non-coding RNA-cyclooxygenase-2; LPS, lipopolysaccharide; miR, micro-RNA; PPARα, nef, negative regulatory factor; peroxisome proliferator-activated receptor alpha; SEMA3A, semaphorin 3A; SOD1, superoxide dismutase 1; Tat, trans-activator of transcription; TDP-43, transactive response (TAR) DNA binding protein; TLR-7, toll-like receptor-7.