Title:Alzheimer’s Disease and other Tauopathies: Exploring Efficacy of Medicinal
Plant-derived Compounds in Alleviating Tau-mediated Neurodegeneration
Volume: 15
Author(s): Siva Sundara Kumar Durairajan*, Karthikeyan Selvarasu, Minu Rani Bera, Kaushik Rajaram, Ashok Iyaswamy and Min Li
Affiliation:
- Mycobiology and Neurodegenerative Disease Research Lab, Department of Microbiology, School of Life Sciences,
Central University of Tamil Nadu, Tiruvarur, India
Keywords:
Alzheimer’s disease, tauopathies, natural compounds, mechanism of action, Tau kinase inhibitors, Tau aggregation inhibitors, HSP90 chaperone modulators, autophagy enhancers.
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, microtubule
(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 plant-
derived compounds capable of modulating the Tau protein, which is significantly elevated and hyperphosphorylated
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, coumarins,
alkaloids, and iridoids, which have been scientifically proven to be Tau-targeting candidates
for the treatment of AD.
