# Terpenes as Potential Anti-Alzheimer's Disease Agents
## 1 Introduction
Due to their dynamic instability nature, MTs can change rapidly and produce a variety of different arrays within cells. The presence of different tubulin isoforms, post-translational modifications (PTMs), and interactions with MT-associated proteins (MAPs) regulates MT morphology and stability, and thus, their function in different cell types [20]. Dysfunctions in the MT system are related to the appearance of several neurodegenerative tauopathies including AD [21]. As a result, MT stabilization may also potentially prevent AD progression. AD prevention also occurs by reducing \(\tau\)-protein phosphorylation, thus avoiding MT dysfunction [22, 23]. Since the degree of \(\tau\)-protein phosphorylation reflects a balance between the competing actions of protein kinases and phosphatases, kinase inhibitors restrain the processes of aggregation and the formation of NFTs [24, 25, 26]. Thus, another promising strategy to combat AD is the inhibition of these protein kinases [25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37]. The most important protein kinase that is involved in \(\tau\)-protein phosphorylation, and thus NFT formation, is the glycogen synthetase kinase-3 beta (GSK3B) [11, 15]. The inflammatory response of microglial cells is another key hallmark of AD pathology [38, 39]. Microglia, the brain's resident immune cells [40], upon stimulation can convert themselves, enabling their phagocytic functions and releasing a diversity of proinflammatory factors (P-IFs), including tumor necrosis factor-\(\alpha\) (TNF-\(\alpha\)), interleukins 1 and 6 (IL-1 and IL-6), reactive oxygen species (ROS), nitric oxide (NO), prostaglandin E2 (PGE2), and cyclooxygenase-2 (COX-2) [41, 42, 43]. Accumulation of these P-IFs results in damage and degeneration of nearby neurons. Then, the damaged neurons release certain immune substances, increasing the inflammatory neurotoxicity and causing irreversible neuroinflammation [44, 45, 46]. Therefore, another potential therapeutic strategy to combat AD is the use of inhibitors of microglia response. Cognitive or memory-related impairments in AD patients are associated with the deficiency of the brain neurotransmitter acetylcholine (ACh). Nevertheless, upon action of acetylcholinesterase enzymes enzyme (AChE), ACh breaks down into acetate and choline. Then, choline is up taken into the presynaptic neuron and carried out by choline carriers, and the signal transduction at the neuromuscular junction finishes rapidly [47]. AChE inhibition prevents the hydrolysis of ACh, increasing its concentration and duration of action, which is clinically beneficial for AD patients. Therefore, AChE inhibitors are widely used for the AD treatment [48]. On the other hand, ACh binds to several receptors in the synaptic cleft. One of them, the nicotinic ACh receptor (nAChR) in the central nervous system, controls the liberation of other neurotransmitters that are involved in cognitive processes and memory [48; 49]. Thus, another strategy to combat AD is controlling nAChRs. AD pathology can thus progress through different pathways which can even be related. For example, AChE accelerates A\(\beta\) formation [50]. Furthermore, the interaction between AChE and A\(\beta\) deposits produces the AChE-A\(\beta\) complex, a very toxic substance, which in turn increases the intracellular calcium load and decreases mitochondrial membrane potential. The AChE-A\(\beta\) complex formation causes neuronal cells' death [51]. AChE also stimulates the protein kinase C (PKC), which inhibits GSK3\(\beta\). Thus, the above mechanisms may work together through interaction between genetic, molecular, and cellular events [52]. Among several strategies that have been identified to combat AD, multi-target drug ligands (MTDLs) represent an effective strategy for the treatment of this multifactorial disease, as compared to single-targeted agents and combined therapy [53]. For example, neuroinflammation and deficit of cholinergic activities are considered major contributing factors for AD.