**12. Conclusion**

In summary, ACh has maintained its importance in etiology and progression of various neurodegenerative diseases. Although the relevance of mAChRs and their exploitation was the predominant mode of cholinergic intervention in various disorders, including neurodegenerative diseases, the advent of nicotinic receptors and their prominent role in many important CNS functions, including cognitive behaviors such as learning, and memory has opened novel therapeutic potentials. This is not only applicable to neurodegenerative diseases such as AD and PD but also to neuropsychiatric disorders such as depression and schizophrenia. Moreover, significant interaction between these 2 distinct classes of receptors occurs. For example, as depicted in **Figure 2**, Aβ, a culprit protein in AD interacts with both receptors albeit at different locations and different cells (e.g., neuronal vs. glial). Despite notable advancements in our knowledge of these receptors, the complexity of cholinergic system in general, and nicotinic system in particular, requires further investigation on specific role of receptor subtypes in health and disease. Notedly, it is argued that pulsatile administration of nicotine or nicotinic agonists-modulators should be considered in any neurodegenerative and/or neuropsychiatric disease. This is due to the complex pharmacokinetic and pharmacodynamic interactions of nicotine with its receptors, where continuous exposure to nicotine (e.g., via patch) may lead to receptor desensitization, whereas pulsatile administration allows functional recovery of the receptor and hence further stimulation. As our understanding of cholinergic system evolves, more therapeutic targets for neurodegenerative and/or neuropsychiatric diseases are anticipated.
