Anti-amyloidogenic amphipathic arginine-dehydrophenylalanine spheres capped selenium nanoparticles as potent therapeutic moieties for Alzheimer's disease

Aggregation of both amyloid beta (Aβ) peptide and hyperphosphorylated tau proteins is the major pathological hallmark of Alzheimer's disease (AD). Moieties that carry anti-amyloidogenic potency against both of the aggregating entities are considered to be promising drug candidatures for the disease. In the current work, we have synthesized amphipathic dipeptide vesicle-templated selenium nanoparticles (RΔF-SeNPs) as potential entities to combat AD. We have investigated and established their anti-amyloidogenic activity against different peptide-based amyloid models, such as the reductionist model based on the dipeptide phenylalanine-phenylalanine (FF) derived from Aβ; a model based on the hexapeptide Ac-PHF6 (306VQIVYK311) derived from tau protein; and the full-length Aβ42 polypeptide-based model. We also evaluated the neuroprotective characteristics of RΔF-SeNPs against FF, Ac-PHF6, and Aβ42 fibril-induced toxicity in neuroblastoma, SH-SY5Y cells. RΔF-SeNPs further exhibited neuroprotective effects in streptozotocin (STZ) treated neuronal (N2a) cells carrying AD-like features. In addition, studies conducted in an intra-cerebroventricular STZ-instigated rat model of dementia revealed that RΔF-SeNP-treated animals showed improved cognitive activity and reduced Aβ42 aggregate burden in brain tissues as compared with the STZ-treated group. Moreover, in vivo brain distribution studies conducted in animal models additionally demonstrated the brain-homing ability of RΔF-SeNPs. All together, these studies supported the potency of RΔF-SeNPs as efficient and propitious disease-modifying therapeutic agents for combating AD.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:15

Enthalten in:

Nanoscale - 15(2023), 30 vom: 03. Aug., Seite 12748-12770

Sprache:

Englisch

Beteiligte Personen:

Kour, Avneet [VerfasserIn]
Tiwari, Virendra [VerfasserIn]
Aggarwal, Nidhi [VerfasserIn]
Sekhar Panda, Himanshu [VerfasserIn]
Kumar, Ashwani [VerfasserIn]
Tiwari, Siddharth [VerfasserIn]
Chauhan, Virander Singh [VerfasserIn]
Shukla, Shubha [VerfasserIn]
Panda, Jiban Jyoti [VerfasserIn]

Links:

Volltext

Themen:

47E5O17Y3R
5W494URQ81
7060-39-1
94ZLA3W45F
Amyloid beta-Peptides
Arginine
Dipeptides
H6241UJ22B
Journal Article
Peptide Fragments
Phenylalanine
Phenyldehydroalanine
Selenium
Streptozocin

Anmerkungen:

Date Completed 04.08.2023

Date Revised 04.08.2023

published: Electronic

Citation Status MEDLINE

doi:

10.1039/d3nr01558k

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM359777104