Details

Autor(en) / Beteiligte

• Jeon, Seong Gak
• Cha, Moon-Yong
• Kim, Jin-il
• Hwang, Tae Woong
• Kim, Kyoung Ah
• Kim, Tae Hyoung
• Song, Ki Chang
• Kim, Jwa-Jin
• Moon, Minho

Titel

Vitamin D-binding protein-loaded PLGA nanoparticles suppress Alzheimer's disease-related pathology in 5XFAD mice

Ist Teil von

• Nanomedicine, 2019-04, Vol.17, p.297-307

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• The aggregation and accumulation of amyloid beta (Aβ) peptide is believed to be the primary cause of Alzheimer's disease (AD) pathogenesis. Vitamin D-binding protein (DBP) can attenuate Aβ aggregation and accumulation. A biocompatible polymer poly (D,L-lactic acid-co-glycolic acid) (PLGA) can be loaded with therapeutic agents and control the rate of their release. In the present study, a PLGA-based drug delivery system was used to examine the therapeutic effects of DBP-PLGA nanoparticles in Aβ-overexpressing (5XFAD) mice. DBP was loaded into PLGA nanoparticles and the characteristics of the DBP-PLGA nanoparticles were analyzed. Using a thioflavin-T assay, we observed that DBP-PLGA nanoparticles significantly inhibited Aβ aggregation in vitro. In addition, we found that intravenous injection of DBP-PLGA nanoparticles significantly attenuated the Aβ accumulation, neuroinflammation, neuronal loss and cognitive dysfunction in the 5XFAD mice. Collectively, our results suggest that DBP-PLGA nanoparticles could be a promising therapeutic candidate for the treatment of AD. A schematic illustration of the proposed therapeutic mechanisms mediated by DBP-loaded PLGA nanoparticles. Aβ monomers spontaneously aggregate into Aβ oligomers and Aβ plaques. The aggregation to oligomers of Aβ causes neuroinflammation, neuronal death, and cognitive deficits in AD. DBP released from PLGA nanoparticles may inhibit the Aβ aggregation and binding of Aβ to neurons, resulting in attenuation of Aβ-mediated pathologies in 5XFAD mice. [Display omitted]