Drugs for Targeted Therapies of Alzheimer's Disease

Curr Med Chem. 2019;26(2):335-359. doi: 10.2174/0929867325666180430150940.

Abstract

Alzheimer's disease (AD) is one type of neurodegenerative diseases, which is prevalent in the elderly. Beta-amyloid (Aβ) plaques and phosphorylated tau-induced neurofibrillary tangles are two pathological hallmarks of this disease and the corresponding pathological pathways of these hallmarks are considered as the therapeutic targets. There are many drugs scheduled for pre-clinical and clinical trial that target to inhibit the initiators of pathological Aβ and tau aggregates as well as critical Aβ secretases and kinases in tau hyperphosphorylation. In addition, studies in disease gene variations, and detection of key prognostic effectors in early development are also important for AD control. The discovery of potential drug targets contributed to targeted therapy in a stage-dependent manner, However, there are still some issues that cause concern such as the low bioavailability and low efficacy of candidate drugs from clinical trial reports. Therefore, modification of drug candidates and development of delivery agents are essential and critical. With other medical advancements like cell replacement therapy, there is hope for the cure of Alzheimer's disease in the foreseeable future.

Keywords: Aβ aggregation; Aβ plaque; drug delivery; neurofibrillary tangles; targeted therapy; tau kinases; tau phosphorylation..

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Alzheimer Disease / therapy*
  • Amyloid / drug effects
  • Amyloid beta-Peptides / immunology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Antibodies, Monoclonal, Humanized / immunology*
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Neuroprotective Agents / therapeutic use*
  • Phosphorylation
  • Protein Multimerization / drug effects
  • tau Proteins / immunology
  • tau Proteins / metabolism

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Antibodies, Monoclonal, Humanized
  • Enzyme Inhibitors
  • Neuroprotective Agents
  • tau Proteins