Alzheimer's Disease (AD) is a fatal neurodegenerative disorder, having a complex aetiology
with numerous possible drug targets. There are targets that have been known for years while
more new targets and theories have also emerged. Beta amyloid and cholinesterases are the most significant
biological targets for finding curative treatment of AD. The major class of drugs used for AD
till now has been the Cholinesterase (ChE) inhibitors. Other prevailing models of molecular pathogenesis
in AD include Neurofibrillary Tangles (NFTs) and amyloid deposition, tryptophan degradation
pathway, kinase and phosphatase activity imbalance and neuroinflammation. The beta amyloid
aggregation initiates flow of events resulting in neurotoxicity and finally clinical pathogenesis of AD.
Furthermore, ApoE is another very significant entity involved in repairing and maintaining the neurons
and has important role in neurodegeneration. Neuroinflammation being the primmest symptom
for AD is essential to focus on. Multiple factors and complexity in interlinking disease progression
pose huge challenge to find one complete curing drug. With so many promising molecules having
multiform pharmacological profile from all over the world however facing failures in clinical trials
indicates the need to consider all aspects of the old as well as new therapeutic targets of AD. Until the
disease mechanism is better understood, it is likely that multiple targeting, symptomatic and diseasemodifying,
is the way forward. Most recent approaches to find anti-Alzheimer's agents have focused
on multi-target directed agents that include targeting all glorious targets hypothesized against AD.
New identification of prototype candidates that could be starting point of a new way of thinking drug
design has been done and many drug candidates are under preclinical evaluation. The main focus of
this review is to discuss the recent understanding of key targets and the development of potential
therapeutic agents for the treatment of AD. It also documents the current therapeutic agents in clinical
trials and under development based on their main mode of action.
Keywords: Alzheimer's disease, Neuroinflammation, Neurofibrillary tangles, Drug targets, Cholinesterase
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