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

Mitra Pirhaghi, Fatemeh Mamashli, Faezeh Moosavi-Movahedi, Payam Arghavani, Ahmad Amiri, Bagher Davaeil, Mahya Mohammad-Zaheri, Zahra Mousavi-Jarrahi, Deepak Sharma, Ülo Langel, Daniel Erik Otzen*, Ali Akbar Saboury*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperReviewResearchpeer-review


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.

Original languageEnglish
JournalMolecular Pharmaceutics
Pages (from-to)2097-2117
Number of pages21
Publication statusPublished - May 2024


  • Alzheimer’s disease (AD)
  • Parkinson’s disease (PD)
  • cell-penetrating peptides
  • central nervous system disorders
  • drug delivery
  • peptide-nanoparticle conjugate
  • Parkinson Disease/drug therapy
  • Humans
  • Blood-Brain Barrier/metabolism
  • Animals
  • Cell-Penetrating Peptides/chemistry
  • Neurodegenerative Diseases/drug therapy
  • Alzheimer Disease/drug therapy
  • Nanoparticles/chemistry
  • Drug Delivery Systems/methods


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