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Molecular drug targets and therapies for Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by normal memory loss and cognitive impairment in humans. Many drug targets and disease-modulating therapies are available for treatment of AD, but none of these are effective enough in reducing problems associated with recognition and memory. Potential drug targets so far reported for AD are β-secretase, Γ-secretase, amyloid beta (Aβ) and Aβ fibrils, glycogen synthase kinase-3 (GSK-3), acyl-coenzyme A: cholesterol acyl-transferase (ACAT) and acetylcholinesterase (AChE). Herbal remedies (antioxidants) and natural metal-chelators have shown a very significant role in reducing the risk of AD, as well as lowering the effect of Aβ in AD patients. Researchers are working in the direction of antisense and stem cell-based therapies for a cure for AD, which mainly depends on the clearance of misfolded protein deposits — including Aβ, tau, and alpha-synuclein. Computational approaches for inhibitor designing, interaction analysis, principal descriptors and an absorption, distribution, metabolism, excretion and toxicity (ADMET) study could speed up the process of drug development with higher efficacy and less chance of failure. This paper reviews the known drugs, drug targets, and existing and future therapies for the treatment of AD.

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Correspondence to Krishna Misra.

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Singh, D.B., Gupta, M.K., Kesharwani, R.K. et al. Molecular drug targets and therapies for Alzheimer’s disease. Translat.Neurosci. 5, 203–217 (2014). https://doi.org/10.2478/s13380-014-0222-x

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Keywords

  • Alzheimer’s disease
  • Amyloid β
  • Tau protein
  • Amyloid precursor protein
  • β and Γ-secretases
  • Glycogen synthase kinase-3
  • Acyl-coenzyme A: cholesterol acyl-transferase (ACAT)