Alzheimer's Disease and other Tauopathies: Exploring Efficacy of Medicinal Plant-Derived Compounds in Alleviating Tau-Mediated Neurodegeneration

Siva Sundara Kumar Durairajan*, Karthikeyan Selvarasu, Minu Rani Bera, Kaushik Rajaram, Ashok Iyaswamy, Min Li

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)

Abstract

Alzheimer’s disease (AD), a major form of dementia, has been reported to affect more than 50 million people worldwide. It is characterized by the presence of amyloid-β (Aβ) plaques and hyperphosphorylated Tau-associated neurofibrillary tangles in the brain. Apart from AD, mi-crotubule (MT)-associated protein Tau is also involved in other neurodegenerative diseases called tauopathies, including Pick’s disease, frontotemporal lobar degeneration, progressive supranuclear palsy, and corticobasal degeneration. The recent unsuccessful phase III clinical trials related to Aβ-targeted therapeutic drugs have indicated that alternative targets, such as Tau, should be studied to discover more effective and safer drugs. Recent drug discovery approaches to reduce AD-related Tau pathologies are primarily based on blocking Tau aggregation, inhibiting Tau phosphorylation, compensating impaired Tau function with MT-stabilizing agents, and targeting the degradation pathways in neuronal cells to degrade Tau protein aggregates. Owing to several limitations of the currently available Tau-directed drugs, further studies are required to generate further effective and safer Tau-based disease-modifying drugs. Here, we review the studies focused on medicinal plan-t-derived compounds capable of modulating the Tau protein, which is significantly elevated and hy-perphosphorylated in AD and other tauopathies. We have mainly considered the studies focused on Tau protein as a therapeutic target. We have reviewed several pertinent papers retrieved from PubMed and ScienceDirect using relevant keywords, with a primary focus on the Tau-targeting compounds from medicinal plants. These compounds include indolines, phenolics, flavonoids, cou-marins, alkaloids, and iridoids, which have been scientifically proven to be Tau-targeting candidates for the treatment of AD.

Original languageEnglish
Pages (from-to)361-379
Number of pages19
JournalCurrent Molecular Pharmacology
Volume15
Issue number2
DOIs
Publication statusPublished - Apr 2022

Scopus Subject Areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

User-Defined Keywords

  • Alzheimer’s disease
  • autophagy enhancers
  • HSP90 chaperone modulators
  • mechanism of action
  • natural compounds
  • Tau aggregation inhibitors
  • Tau kinase inhibitors
  • tauopathies

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