More possibilities from Rivastigmine to new potential agents on treating Alzheimer's disease: In silico study

Abstract

Along with the development of the modern world, advanced medicinal and therapeutic conditions have encouraged longevity to be the common sense [1]. Concomitantly, the usual defined diseases for elder population, have forced the researchers to face the fact that they are occurring with higher percentages and stretching their claws to younger people [2,3]. Among them, Alzheimer’s disease (AD) is of course one of the most hazardous and frequent, which ruined the capabilities of remembering recent things, organizing language, distinguishing orientations and controlling mood [4,5]. AD is a widely known chronic neurodegenerative disease and it caused a majority of dementia cases (over 60%) [6,7]. On the contrary, the cause of AD is still poorly revealed. Since the major phenomena are amyloid beta (Aβ) deposits, tau protein abnormalities and neuronal death, several hypotheses have been raised accordingly [8-10]: 1) Genetic cause, mainly the mutations in genes encoding amyloid precursor protein (APP) and presenilins 1 and 2 [11]; 2) Cholinergic hypothesis, the most typical one with the most currently available drugs based [12-14]; 3) Amyloid hypothesis, the currently leading opinion in this field but the two developed vaccines Bapineuzumab and Solanezumab both failed the Phase III clinical trials [15-18]; 4) Tau hypothesis, the most accepted target following the amyloid with potential agents on the promotion of Tau’s decomposition and the inhibition of its accumulation or phosphorylation [19-21]; 5) Other hypotheses including inflammation, aluminium, smoking and gum diseases [22-25]. In spite of the antiamyloid vaccine’s failures, the very recent study also questioned the rationality of inhibition Tau because its multiple functions [26]. Thus, acetylcholinesterase inhibitors (AChEI) are still the down-to-earth choices of the patients of AD.