New Drug Design Avenues Targeting Alzheimer's Disease by Pharmacoinformatics-Aided Tools.

Neurodegenerative diseases (NDD) have been of great interest to scientists for a long time due to their multifactorial character. Among these pathologies, Alzheimer's disease (AD) is of special relevance, and despite the existence of approved drugs for its treatment, there is still no efficient pharmacological therapy to stop, slow, or repair neurodegeneration. Existing drugs have certain disadvantages, such as lack of efficacy and side effects. Therefore, there is a real need to discover new drugs that can deal with this problem. However, as AD is multifactorial in nature with so many physiological pathways involved, the most effective approach to modulate more than one of them in a relevant manner and without undesirable consequences is through polypharmacology. In this field, there has been significant progress in recent years in terms of pharmacoinformatics tools that allow the discovery of bioactive molecules with polypharmacological profiles without the need to spend a long time and excessive resources on complex experimental designs, making the drug design and development pipeline more efficient. In this review, we present from different perspectives how pharmacoinformatics tools can be useful when drug design programs are designed to tackle complex diseases such as AD, highlighting essential concepts, showing the relevance of artificial intelligence and new trends, as well as different databases and software with their main results, emphasizing the importance of coupling wet and dry approaches in drug design and development processes.

Anatomical root variations in response to water deficit: wild and domesticated common bean (Phaseolus vulgaris L)

Root anatomical responses to water deficit are diverse and regulation of water uptake strongly depends on plant anatomy. The ancestors of common bean (Phaseolus vulgaris L.) cultivars are the wild common beans. Because wild beans adapt and survive well in theon atural environment, it is hypothesized that wild common bean roots are less affected than those of domesticated beans at low substrate water potential (ψW). A wild common bean accession from Chihuahua Mexico and cv. Bayomex were studied. Seedlings with a mean root length between 3 and 4 cm were maintained for 24 h in vermiculite at ψW of -0.03 (well hydrated), -0.65, -1.48 and -2.35 MPa (partially dry). Ten anatomical characteristics of differentiation and cell division in root regions were evaluated. Thickness of epidermis and protoderm diminished similarly in wild and domesticated beans growing at low substrate ψW (between -0.65 and -2.35 MPa). At the same time, parenchymatic cell area diminished by 71 percent in the domesticated variety, but by only 32 percent in the wild bean at -2.35 MPa. Theon umber of cells in the cortex and the thickness of the xylem wall increased in both wild and domesticated beans at low substrate ψW;on evertheless, the effect was significantly lower in the wild bean. Theon umber of xylem vessels increased in the cultivar (up to 40 percent) while in the wild bean it decreased (up to 33 percent). The diameter of xylem vessels and transverse root area diminished (15 and 57 percent, respectively) in the cultivar, but in the wild common bean wereon ot affected. Anatomical root characteristics and their modifications in both differentiation and cell division in root regions demonstrated that the wild bean reacted quite differently to substrate ψW than the domesticated common bean.