The Role of Exosomal microRNAs and Oxidative Stress in Neurodegenerative Diseases

Figure 3

Exosomes and miRNA regulatory network in neurodegenerative diseases. (1) The major cause of AD, PD, and HD is abnormal aggregation of Aβ, α-syn, and mHtt in neurons. Neuronal cells can release exosomes into the extracellular space or transport them to surrounding cells via the bloodstream. (2) Exosomes contain miRNA. Following exosomes fuse with the membrane and release miRNA into the intracellular plasma membrane, TLRs are activated. TLR7-9 activates MyD88, which then activates NF-κB and AP-1, leading to neuroinflammation and neuronal death. (3) The disorders in miRNA generation play role in neurodegenerative diseases, including absence of Dicer. The absence of Dicer contributes to Aβ accumulation and dopamine loss. TDP-43 could combine with Drosha, and it could be seen in ALS models. miRNAs: microRNAs; Aβ: amyloid-β peptide; α-syn: α-synuclein; mHtt: mutated Huntingtin; AD: Alzheimer’s disease; PD: Parkinson’s disease; HD: Huntington’s disease; TLR: toll-like receptor; MyD88: myeloid differentiation factor NF-κB, nuclear factor-κB; AP-1: transcription factor activator protein-1; ALS: amyotrophic lateral sclerosis; TDP-43: transactivating response region DNA-binding protein 43.