Precise Modulation of Pericyte Dysfunction by a Multifunctional Nanoprodrug to Ameliorate Alzheimer's Disease.
ACS Nano
; 18(22): 14348-14366, 2024 Jun 04.
Article
en En
| MEDLINE
| ID: mdl-38768086
ABSTRACT
Pericyte dysfunction severely undermines cerebrovascular integrity and exacerbates neurodegeneration in Alzheimer's disease (AD). However, pericyte-targeted therapy is a yet-untapped frontier for AD. Inspired by the elevation of vascular cell adhesion molecule-1 (VCAM-1) and reactive oxygen species (ROS) levels in pericyte lesions, we fabricated a multifunctional nanoprodrug by conjugating the hybrid peptide VLC, a fusion of the VCAM-1 high-affinity peptide VHS and the neuroprotective apolipoprotein mimetic peptide COG1410, to curcumin (Cur) through phenylboronic ester bond (VLC@Cur-NPs) to alleviate complex pericyte-related pathological changes. Importantly, VLC@Cur-NPs effectively homed to pericyte lesions via VLC and released their contents upon ROS stimulation to maximize their regulatory effects. Consequently, VLC@Cur-NPs markedly increased pericyte regeneration to form a positive feedback loop and thus improved neurovascular function and ultimately alleviated memory defects in APP/PS1 transgenic mice. We present a promising therapeutic strategy for AD that can precisely modulate pericytes and has the potential to treat other cerebrovascular diseases.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Ratones Transgénicos
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Pericitos
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Enfermedad de Alzheimer
Límite:
Animals
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Humans
Idioma:
En
Revista:
ACS Nano
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ACS nano
Año:
2024
Tipo del documento:
Article