Cell-Penetrating Peptides: Promising Therapeutics and Drug-Delivery Systems for Neurodegenerative Diseases

Abstract

Currently, one of the most significant and rapidly growing unmet medical challenges is the treatment of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). This challenge encompasses the imperative development of efficacious therapeutic agents and overcoming the intricacies of the blood−brain barrier for successful drug delivery. Here we focus on the delivery aspect with particular emphasis on cell-penetrating peptides (CPPs), widely used in basic and translational research as they enhance drug delivery to challenging targets such as tissue and cellular compartments and thus increase therapeutic efficacy. The combination of CPPs with nanomaterials such as nanoparticles (NPs) improves the performance, accuracy, and stability of drug delivery and enables higher drug loads. Our review presents and discusses research that utilizes CPPs, either alone or in conjugation with NPs, to mitigate the pathogenic effects of neurodegenerative diseases with particular reference to AD and PD.

Reduction in Hippocampal Amyloid-β Peptide (Aβ) Content during Glycine-Proline-Glutamate (Gly-Pro-Glu) Co-Administration Is Associated with Changes in Inflammation and Insulin-like Growth Factor (IGF)-I Signaling

“…This study shows that the deleterious effects of Aβ on SRIF functionality are blocked by GPE. Although the regulatory mechanisms of SRIF tone are partially unknown, both our previous results [ 13 ] and the new data included in this study suggest that the activation of leptin and IGF-I signaling may be involved in the protective effect of GPE on this neurotransmitter. Leptin may be involved in the preservation of SRIF cells against Aβ effects as this adipokine protects against Aβ-induced cell death through a STAT3-dependent mechanism [ 53 ].…”

“…Neurodegenerative diseases are a serious health concern worldwide, with a high incidence due to increasing life expectancy and the lack of restorative treatments. Therapies based on the use of different proteins have emerged as a possible strategy due to their high specificity and activity on different biological targets [ 13 ]. Several endogenous peptides have anti-apoptotic and neuroprotective properties in the central nervous system, among which glycine-proline-glutamate (GPE), a natural peptide cleaved from the N-terminus of insulin-like growth factor I (IGF)-I, is a protective agent in brain injury [ 14 ] and has shown neuroprotective capabilities in experimental models of AD [ 15 , 16 ].…”

Reduction in Hippocampal Aβ Content During Gly-Pro-Glu Co-Administration Is Associated with Changes in Inflammation and IGF-I Signaling

“…Neurodegenerative diseases are a serious health concern worldwide, with a high incidence due to increasing life expectancy and the lack of restorative treatments. Therapies based on the use of different proteins have emerged as a possible strategy due to their high specificity and activity on different biological targets [11]. Several endogenous peptides have anti-apoptotic and neuroprotective properties in the central nervous system and among which, glycine-prolineglutamate (GPE) a natural peptide cleaved from the N-terminus of insulin-like growth factor I (IGF)-I, is a protective agent in brain injury [12] and has shown neuroprotective capabilities in experimental models of AD [13,14].…”