Abstract
Animal studies have indicated that increased blood-brain barrier (BBB) permeability and inflammatory cell infiltration are involved during the progression of Parkinson’s disease (PD). This study used C16, a peptide that competitively binds to integrin αvβ3 and inhibits inflammatory cell infiltration, as well as angiopoietin-1 (Ang-1), an endothelial growth factor crucial for blood vessel protection, to reduce inflammation and improve the central nervous system (CNS) microenvironment in murine models of PD. The combination of C16 and Ang-1 yielded better results compared to the individual drugs alone in terms of reducing dopaminergic neuronal apoptosis, ameliorating cognitive impairment, and electrophysiological dysfunction, attenuating inflammation in the CNS microenvironment, and improving the functional disability in PD mice or rats. These results suggest neuroprotective and anti-inflammatory properties of the C16 peptide plus Ang-1 in PD.
Highlights
Neuroinflammation, referring to inflammation in the nervous system, is associated with many neurodegenerative diseases, such as Parkinson’s disease (PD), amyotrophic lateral sclerosis, Alzheimer’s disease, and Huntington’s disease[1]
C16 or Ang-1 alone ameliorated functional impairment in PD animals, while the combination of C16 and Ang-1 exhibited more potent therapeutic effects including a reduction in the mean velocity of both animal models in the open field test, decreased distance traveled in 6-OHDA-treated rats, and increased time on the rotarod test device in MPTP-treated mice (Fig. 1a–f)
Oxidative stress leads to excessive production of reactive oxygen species (ROS), which chemically interact with biological molecules, resulting in functional changes in cells and cell death
Summary
Neuroinflammation, referring to inflammation in the nervous system, is associated with many neurodegenerative diseases, such as Parkinson’s disease (PD), amyotrophic lateral sclerosis, Alzheimer’s disease, and Huntington’s disease[1]. Inflammatory mediator-induced neurotoxicity has been recognized as a major contributor to neurodegenerative diseases, a breakdown of the blood-brain barrier (BBB) has been implicated in PD progression[2]. Angiopoietin-1 (Ang-1) is an agonist ligand for the Tie-2 receptor that inhibits inflammatory cell infiltration and ameliorates inflammation-induced vessel leakage in the central nervous system (CNS)[4]. The Ang-1/Tie-2/non-receptor protein tyrosine phosphatase pathway has been shown to prevent BBB breakdown by maintaining occludin in a dephosphorylated state, providing a novel therapeutic pathway to prevent vessel leakage associated with neuro-inflammatory disorders[4]
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