Combating Dopaminergic Neurodegeneration in Parkinson's Disease through Nanovesicle Technology

ACS Chem Neurosci. 2023 Aug 16;14(16):2830-2848. doi: 10.1021/acschemneuro.3c00070. Epub 2023 Aug 3.

Abstract

Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration, resulting in dopamine depletion and motor behavior deficits. Since the discovery of L-DOPA, it has been the most prescribed drug for symptomatic relief in PD, whose prolonged use, however, causes undesirable motor fluctuations like dyskinesia and dystonia. Further, therapeutics targeting the pathological hallmarks of PD including α-synuclein aggregation, oxidative stress, neuroinflammation, and autophagy impairment have also been developed, yet PD treatment is a largely unmet success. The inception of the nanovesicle-based drug delivery approach over the past few decades brings add-on advantages to the therapeutic strategies for PD treatment in which nanovesicles (basically phospholipid-containing artificial structures) are used to load and deliver drugs to the target site of the body. The present review narrates the characteristic features of nanovesicles including their blood-brain barrier permeability and ability to reach dopaminergic neurons of the brain and finally discusses the current status of this technology in the treatment of PD. From the review, it becomes evident that with the assistance of nanovesicle technology, the therapeutic efficacy of anti-PD pharmaceuticals, phyto-compounds, as well as that of nucleic acids targeting α-synuclein aggregation gained a significant increment. Furthermore, owing to the multiple drug-carrying abilities of nanovesicles, combination therapy targeting multiple pathogenic events of PD has also found success in preclinical studies and will plausibly lead to effective treatment strategies in the near future.

Trial registration: ClinicalTrials.gov NCT04976127.

Keywords: Neurotrophin; aptamer; baicalein; cerasome; ubiquitin−proteasome; α-synuclein.

Publication types

  • Review

MeSH terms

  • Brain / metabolism
  • Dopamine / pharmacology
  • Dopaminergic Neurons / metabolism
  • Humans
  • Levodopa / pharmacology
  • Levodopa / therapeutic use
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / pathology
  • alpha-Synuclein / metabolism

Substances

  • alpha-Synuclein
  • Dopamine
  • Levodopa

Associated data

  • ClinicalTrials.gov/NCT04976127