Potential use of miRNA-transfected exosomes in Alzheimer's disease treatment
FEBS OPEN BIO, cilt.16, sa.SI, ss.265, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Özet
- Cilt numarası: 16 Sayı: SI
- Basım Tarihi: 2026
- Dergi Adı: FEBS OPEN BIO
- Derginin Tarandığı İndeksler: Applied Science & Technology Source, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Scopus, Science Citation Index Expanded (SCI-EXPANDED), BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Directory of Open Access Journals
- Sayfa Sayıları: ss.265
- Hacettepe Üniversitesi Adresli: Evet
Özet
Rationale: The neuropathological hallmarks of Alzheimer’s disease (AD) involve the accumulation of amyloid- (A ) plaques and neurofibrillary tangles made of tau protein, occurring extracellularly and intracellularly, respectively. Current therapeutic approaches may temporarily improve neuronal communication and reduce symptom severity; however, they do not offer a permanent cure for AD. Inhibiting the A (1 40) and A (1 42) variants could slow disease progression. Many miRNAs linked to AD have been identified in the literature, but their therapeutic use remains limited due to constraints and stability issues. Evidence shows that exosomes can effectively deliver various cargos to target cells, making these naturally derived nanovesicles suitable carriers for drug and gene delivery. A major challenge in AD treatment is the highly selective and restrictive permeability of the blood brain barrier (BBB). It is known that exosomes can cross the BBB, which is the primary obstacle in brain-related disorders.
Methods: In this study, miRNA mimics and inhibitors were transfected into exosomes for AD therapy. In vitro transfection and cytotoxicity assays were performed. The ability of exosomes to cross the BBB was demonstrated using an in vitro BBB model. Fibrils were formed and the inhibitory effects of miRNA-loaded exosomes on fibril aggregation were assessed.
Results: As a result, miRNA transfection efficiency was enhanced through exosome-mediated delivery. It was also shown that miRNA-loaded exosomes exhibited no cytotoxicity in astrocyte and brain endothelial cell lines (p 0.05). Approximately 90 4,1% of both single and combined miRNA-loaded exosomes crossed the BBB within 24 hours. The unchanged fluorescence of A (1 40) and A (1 42) peptides in the presence of miRNA-loaded exosomes indicates inhibition of fibril formation.
Conclusions: Future studies will evaluate the therapeutic efficacy of miRNA-loaded exosomes at the gene and protein levels in an in vitro BBB-based AD model.
Funding: This study was supported by The Scientific and Technological Research Council of Turkiye (TUBITAK) under project number 223S779.