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

Mol Pharm. 2024 May 6;21(5):2097-2117. doi: 10.1021/acs.molpharmaceut.3c01167. Epub 2024 Mar 5.

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.

Keywords: Alzheimer’s disease (AD); Parkinson’s disease (PD); cell-penetrating peptides; central nervous system disorders; drug delivery; peptide-nanoparticle conjugate.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / drug therapy
  • Animals
  • Blood-Brain Barrier* / drug effects
  • Blood-Brain Barrier* / metabolism
  • Cell-Penetrating Peptides* / administration & dosage
  • Cell-Penetrating Peptides* / chemistry
  • Drug Delivery Systems* / methods
  • Humans
  • Nanoparticles* / chemistry
  • Neurodegenerative Diseases* / drug therapy
  • Parkinson Disease* / drug therapy

Substances

  • Cell-Penetrating Peptides