Microorganism-Derived Molecules as Enzyme Inhibitors to Target Alzheimer’s Diseases Pathways

Abstract

Alzheimer’s disease (AD) is the most common form of dementia. It increases the risk of other serious diseases and causes a huge impact on individuals, families, and socioeconomics. AD is a complex multifactorial disease, and current pharmacological therapies are largely based on the inhibition of enzymes involved in the pathogenesis of AD. Natural enzyme inhibitors are the potential sources for targeting AD treatment and are mainly collected from plants, marine organisms, or microorganisms. In particular, microbial sources have many advantages compared to other sources. While several reviews on AD have been reported, most of these previous reviews focused on presenting and discussing the general theory of AD or overviewing enzyme inhibitors from various sources, such as chemical synthesis, plants, and marine organisms, while only a few reviews regarding microbial sources of enzyme inhibitors against AD are available. Currently, multi-targeted drug investigation is a new trend for the potential treatment of AD. However, there is no review that has comprehensively discussed the various kinds of enzyme inhibitors from the microbial source. This review extensively addresses the above-mentioned aspect and simultaneously updates and provides a more comprehensive view of the enzyme targets involved in the pathogenesis of AD. The emerging trend of using in silico studies to discover drugs concerning AD inhibitors from microorganisms and perspectives for further experimental studies are also covered here.

Trisubstituted 1,3,5-Triazines and Their Effect on BACE1

“…However, it must be admitted that, based on the latest studies and the situation with the early termination of all clinical trials of the main BACE1 inhibitors such as verubecestat atabecestat, elenbecestat lanabecestat umibecestat, LY2886721, RO5508887 or PF-06751979 by pharmaceutical companies (e.g., Pfizer, AstraZeneca, Merck, Eli Lilly, Roche, Novartis, Janssen, Biogen, Amgen) due to serious side effects or actual ineffectiveness, it is possible to speculate to what extent the development of BACE inhibitors (the β-secretase inhibition hypothesis) represents a dead end, or how long the development of these inhibitors for AD treatment will continue to be preferred by pharmaceutical companies [27,45,46]. On the other hand, natural BACE1 inhibitors with different structures are still being discovered [47] and the role of the Aβ peptide is being investigated in depth [48,49].…”

Proteomic Approach to Anemonia sulcata and Its Symbiont Symbiodinium spp. as New Source of Potential Biotechnological Applications and Climate Change Biomarkers

“…The potential study of marine ecosystems may elucidate new active compounds from a wide variety of organisms and microorganisms to solve problems from Alzheimer’s disease [ 18 ] to, i.e., bacterial infections [ 19 ]. On the other hand, recent developments in proteomics approaches have shown a capacity to unravel complex biological problems.…”

Naturally Occurring Asterric Acid Analogs: Chemistry and Biology

“…The earliest theory proposed for Alzheimer’s disease (AD), the cholinergic hypothesis, suggested that the cause of AD is acetylcholinesterase (AChE)-induced impaired synthesis of the acetylcholine neurotransmitter. Given that, AChE inhibitors have been proven to be effective therapeutic agents for the treatment of AD . Lately, asterric acid ( 1 ), methyl asterrate ( 3 ), and ethyl asterrate ( 36 ) were explored to be AChE inhibitors.…”

“…Given that, AChE inhibitors have been proven to be effective therapeutic agents for the treatment of AD. 84 Lately, asterric acid (1), methyl asterrate (3), and ethyl asterrate (36) were explored to be AChE inhibitors. Researchers supposed that the variety and size of the esterification substituent at C-2 might be critical for the AChE inhibitory activities, considering the result that the IC 50 values of 1, 3, and 36 were 66.7, 23.3, and 20.1 μM, respectively.…”