The central cholinergic system as a therapeutic target in Parkinson's disease

The central cholinergic system plays a crucial role in neural communication and physiological regulation, mediated by acetylcholine (ACh) and cholinergic receptors in the central nervous system (CNS). In this review, we explore the extensive distribution and impact of the central cholinergic system and its pivotal involvement in Parkinson's disease (PD). Despite PD being traditionally perceived as primarily a dopaminergic disorder, it exhibits significant cholinergic alterations, contributing to both motor and non-motor symptoms. These PD-specific alterations manifest as neuroanatomical changes, diminished acetylcholinesterase activity, and functional disturbances across various brain regions, impacting cognition, mood, sensory perception, sleep, and motor function. Comprehension of these cholinergic dysfunctions is paramount for the development of targeted therapies aimed at alleviating these PD symptoms. To provide further insight, we explore the therapeutic potential of nicotinic acetylcholine receptors (nAChRs) in PD, highlighting their role in preventing apoptosis, modulating neuroinflammation, and mitigating CNS damage. In summary, this review underscores the critical importance of cholinergic mechanisms in PD pathology and champions cholinergic-based interventions for enhanced patient outcomes and improved quality of life.