# Terpenes as Potential Anti-Alzheimer's Disease Agents
## 1 Introduction
Thus, compounds that have activity against AChE and anti-inflammatory properties are multi-target compounds able to combat AD. In the last few decades, significant research effort has been devoted to the development of anti-AD agents from natural sources (including plants, microbes, and marine organisms), which are considered to be safer and to have lesser side effects as compared to those of synthetic drugs. In fact, effective drugs approved by the Food and Drug Administration (FDA) of the United States include the AChE inhibitors galanthamine, which is a natural product itself, and rivastigmine, a semi-synthetic derivative of a natural product called physostigmine [54; 55]. Among the natural products, terpenes and their derivatives, i.e., terpenes containing different functional groups (also known as terpenoids), are the largest and the most diverse group of plant secondary metabolites (SMs). Terpenes are composed of multiple isoprene units (C\({}_{5}\)H\({}_{8}\)). Nevertheless, not all terpenes have even numbers of intact isoprene units, and some of them are different, such as the C19 diterpenes (nor-diterpenes) [56]. Others, such as the meroterpenes, are hybrid SMs that derive partially from the terpene pathway [57]. One of the most applied classifications for terpenes is based on the number of five-carbon units (called isoprene units) present in their chemical structure (Figure 1). Hemiterpenes have a scaffold based on one isoprene unit (C5). Monoterpenes present two isoprene units (C10) and express different arrangements, such as acyclic, monocyclic, and bicyclic. Sesquiterpenes, constituted by three isoprene units (C15), are also acyclic or mono-, di-, and tricyclic compounds. Diterpene and triterpene compounds (C20 and C30, respectively) have a wide distribution from many different carbon skeletons. Tetraterpenes (C40) have a large structure, and they are also known as carotenoids [56]. Compared with the referred terpene groups, the sesterterpenes (C25) are the rarest terpene group originating from plant sources. Terpenes are biosynthesized in superior plants from two interconvertible five-carbon precursors, isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP) (Figure 1). IPP and DMAPP are generated from two alternative biosynthetic routes (Figure 1), the cytosolic acetate/mevalonate (MVA) pathway and the plastidic pyruvate/methylerythitol phosphate (MEP) pathway, also known as the non-mevalonate pathway. Terpene synthases (TPSs) are regarded as the critical catalytic enzyme along the terpene biosynthetic pathways. Moreover, the vast types of terpenes arise from the different TPS types present in the plants [54; 56; 58]. Because of their chemical diversity, terpenes play many important functional roles to enhance the plant's overall fitness, thereby fostering their survival in a co-evolving ecosystem. Furthermore, these plant SMs have a widespread industrial application, ranging  
Figure 1: The mevalonate (MVA) and methylerythriold phosphate (MEP) pathways in biosynthesis of plant terpenes. These compounds can be classified by the number of isoprene units (n) present in the chemical structure. from flavors and fragrances (e.g., linalool) to medicines (e.g., Taxol(r) and artemisinin). In fact, to date, many terpenes, mainly from essential oils and plant extracts, as well as forest bathing, have been reported to exhibit a plethora of important bioactivities ranging from antioxidant, anti-inflammatory, and anticancer to neuroprotection properties [54; 55; 58]. As a result, terpenes, mainly obtained from medicinal plants, have a huge potential for being novel, multi-targeted, and low-toxicity anti-AD drugs [55]. Thus, the current review focuses on the several terpenes that have been analyzed for their neuroprotective effects through the mechanisms highlighted below (Figure 2).