Multifaceted Alzheimer's Disease: Building a Roadmap for Advancement of Novel Therapies.Neurochem Res. 2021 Nov; 46(11):2832-2851.NR
Alzheimer's disease (AD) is one of the most prevailing neurodegenerative disorders of elderly humans associated with cognitive damage. Biochemical, epigenetic, and pathophysiological factors all consider a critical role of extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) as pathological hallmarks of AD. In an endeavor to describe the intricacy and multifaceted nature of AD, several hypotheses based on the roles of Aβ accumulation, tau hyperphosphorylation, impaired cholinergic signaling, neuroinflammation, and autophagy during the initiation and advancement of the disease have been suggested. However, in no way do these theories have the potential of autonomously describing the pathophysiological alterations located in AD. The complex pathological nature of AD has hindered the recognition and authentication of successful biomarkers for the progression of its diagnosis and therapeutic strategies. There has been a significant research effort to design multi-target-directed ligands for the treatment of AD, an approach which is developed by the knowledge that AD is a composite and multifaceted disease linked with several separate but integrated molecular pathways.