Graphene quantum dots conjugated neuroprotective peptide improve learning and memory capability

Biomaterials. 2016 Nov:106:98-110. doi: 10.1016/j.biomaterials.2016.08.021. Epub 2016 Aug 17.

Abstract

Alzheimer disease (AD) is a neurodegenerative disorder and the most common form of dementia. Histopathologically is characterized by the presence extracellular neuritic plaques and with a large number of neurons lost. In this paper, we design a new nanomaterial, graphene quantum dots (GQDs) conjugated neuroprotective peptide glycine-proline-glutamate (GQDG) and administer it to APP/PS1 transgenic mice. The in vitro assays including ThT and CD proved that GQDs and GQDG could inhibit the aggregation of Aβ1-42 fibrils. Morris water maze was performed to exanimate learning and memory capacity of APP/PS1 transgenic mice. The surface area of Aβ plaque deposits reduced in the GQDG group compared to the Tg Ctrl groups. Furthermore, newly generated neuronal precursor cell and neuron were test by immunohistochemical. Besides, neurons were impregnated by DiI using gene gun to show dendritic spine. Results indicated enhancement of learning and memory capacity and increased amounts of dendritic spine were observed. Inflammation factors and amyloid-β (Aβ) were tested with suspension array and ELISA, respectively. Several pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-33, IL-17α, MIP-1β and TNF-α) had decreased in GQDG group compared with Control group. Reversely, anti-inflammatory cytokines (IL-4, IL-10) had increased in GQDG group compared with Control group. Thus, we demonstrate that the GQDG is a promising drug in treatment of neurodegenerative diseases such as AD.

Keywords: Alzheimer disease (AD); Amyloid-β (Aβ); Dendritic spine; Graphene quantum dots; Neuroprotective peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Animals
  • Graphite / chemistry*
  • Learning / drug effects*
  • Male
  • Memory / drug effects*
  • Mice
  • Mice, Transgenic
  • Nanoconjugates
  • Neuroprotective Agents / administration & dosage*
  • Peptides / administration & dosage*
  • Peptides / chemistry
  • Quantum Dots*
  • Treatment Outcome

Substances

  • Nanoconjugates
  • Neuroprotective Agents
  • Peptides
  • Graphite