Targeting the Pathological Hallmarks of Alzheimer's Disease Through Nanovesicleaided Drug Delivery Approach

Curr Drug Metab. 2022;23(9):693-707. doi: 10.2174/1389200223666220526094802.

Abstract

Introduction: Nanovesicle technology is making a huge contribution to the progress of treatment studies for various diseases, including Alzheimer's disease (AD). AD is the leading neurodegenerative disorder characterized by severe cognitive impairment. Despite the prevalence of several forms of anti-AD drugs, the accelerating pace of AD incidence cannot becurbed, and for rescue, nanovesicle technology has grabbed much attention.

Methodology: Comprehensive literature search was carried out using relevant keywords and online database platforms. The main concepts that have been covered included a complex pathomechanism underlying increased acetylcholinesterase (AchE) activity, β-amyloid aggregation, and tau-hyperphosphorylation forming neurofibrillary tangles (NFTs) in the brain, which are amongst the major hallmarks of AD pathology. Therapeutic recommendations exist in the form of AchE inhibitors, along with anti-amyloid and anti-tau therapeutics, which are being explored at a high pace. The degree of the therapeutic outcome, however, gets restricted by the pharmacological limitations. Susceptibility to peripheral metabolism and rapid elimination, inefficiency to cross the blood-brain barrier (BBB) and reach the target brain site are the factors that lower the biostability and bioavailability of anti-AD drugs. The nanovesicle technology has emerged as a route to preserve the therapeutic efficiency of the anti-AD drugs and promote AD treatment. The review hereby aims to summarize the developments made by the nanovesicle technology in aiding the delivery of synthetic and plant-based therapeutics targeting the molecular mechanism of AD pathology.

Conclusion: Nanovesicles appear to efficiently aid in target-specific delivery of anti-AD therapeutics and nullify the drawbacks posed by free drugs, besides reducing the dosage requirement and the adversities associated. In addition, the nanovesicle technology also appears to uplift the therapeutic potential of several phyto-compounds with immense anti-AD properties. Furthermore, the review also sheds light on future perspectives to mend the gaps that prevail in the nanovesicle-mediated drug delivery in AD treatment strategies.

Keywords: Dementia; acetylcholinesterase; beta-amyloid aggregation; curcumin; liposome; osthole; rivastigmine; tau-phosphorylation.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Acetylcholinesterase / therapeutic use
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Humans
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology

Substances

  • Acetylcholinesterase
  • Amyloid beta-Peptides