Unveiling the Multitarget Anti-Alzheimer Drug Discovery Landscape: A Bibliometric Analysis

Abstract

Multitarget anti-Alzheimer agents are the focus of very intensive research. Through a comprehensive bibliometric analysis of the publications in the period 1990–2020, we have identified trends and potential gaps that might guide future directions. We found that: (i) the number of publications boomed by 2011 and continued ascending in 2020; (ii) the linked-pharmacophore strategy was preferred over design approaches based on fusing or merging pharmacophores or privileged structures; (iii) a significant number of in vivo studies, mainly using the scopolamine-induced amnesia mouse model, have been performed, especially since 2017; (iv) China, Italy and Spain are the countries with the largest total number of publications on this topic, whereas Portugal, Spain and Italy are the countries in whose scientific communities this topic has generated greatest interest; (v) acetylcholinesterase, β-amyloid aggregation, oxidative stress, butyrylcholinesterase, and biometal chelation and the binary combinations thereof have been the most commonly pursued, while combinations based on other key targets, such as tau aggregation, glycogen synthase kinase-3β, NMDA receptors, and more than 70 other targets have been only marginally considered. These results might allow us to spot new design opportunities based on innovative target combinations to expand and diversify the repertoire of multitarget drug candidates and increase the likelihood of finding effective therapies for this devastating disease.

A Combined Chronic Low-Dose Soluble Epoxide Hydrolase and Acetylcholinesterase Pharmacological Inhibition Promotes Memory Reinstatement in Alzheimer’s Disease Mice Models

“…Conversely, simultaneous modulation of several targets (multitarget approach) has emerged as a very promising option to efficiently cope with the AD pathological network [ 35 ]. Very intensive research has been done in the last decade for the development of different classes of multitarget agents, i.e., single molecules designed to hit several biological targets [ 36 ]. However, much less attention is being given to the development of combination therapies, i.e., combinations of two or more drugs each one hitting a different biological target.…”

Multitargeting the Action of 5-HT6 Serotonin Receptor Ligands by Additional Modulation of Kinases in the Search for a New Therapy for Alzheimer’s Disease: Can It Work from a Molecular Point of View?

“… General structures ( A , B ) of the potent MARK4 inhibitors (IC 50 < 1 µM) described [ 14 , 15 , 16 , 17 , 18 , 19 ]. The common feature of pyrimidine 2,4,5-trisubstituted ( A ) or 2-substituted-4,5-cyclic ( B ) in blue, the favorable substituents in rectangular frames.…”

“…It is supposed that the clinical failure of 5-HT 6 R agents is a consequence of the fact that those anti-AD drug candidates have been designed as single-target molecules, whereas such a complex disease as AD involves many different signaling pathways that form the pathological network [ 15 ]. Hence, selecting just one target may indeed lead to insufficiency [ 16 ]. Moreover, multidirectional molecules may have a more predictable pharmacokinetic profile than combined therapy with two or more single-target drugs [ 17 , 18 ].…”

A Bibliometric and Visual Analysis of Exercise Intervention Publications for Alzheimer’s Disease (1998–2021)

“…Compared with traditional systematic evaluation and meta-analysis, bibliometric analysis can reveal the present situation and the evolution of research topics from a more systematic and intuitive level. In recent years, some researchers have combed and analyzed the literature on AD-related research from the perspective of bibliometrics, for example, the brain energy metabolism disorder mechanism of AD [ 18 ], publishing trends in AD research [ 19 , 20 ], drug research with regard to AD [ 21 , 22 , 23 ], genetic research on AD [ 24 ], and so on. Specifically, through analyzing the literature from 2000 to 2020, Y.-H. Du et al found that brain energy disorder plays a central role in the occurrence and development of AD.…”