ABSTRACT
Parkinson’s disease (PD) is the second most common idiopathic neurodegenerative disorder, and millions of people around the world have been diagnosed with it. PD is characterized by tremor, bradykinesia, muscle rigidity, impaired gait, and posture. The trademark pathology of PD includes dopaminergic neuronal loss in the substantia nigra pars compacta and depletion of dopamine levels in the striatum. This leads to a perplexing array of clinical features whose identification and management can be challenging for even the most perceptive clinician. The core clinical complex of PD constitutes the four cardinal signs of tremor, bradykinesia, rigidity, and loss of postural reflexes. A variety of additional motor features develop in PD, in addition to these cardinal signs. In recent times, it has been recognized that a number of non-motor features also describe PD. The occurrence of these non-motor features may actually precede the development of the classic motor features. Our understanding of PD has expanded at all levels since its description two centuries ago, from the explanation of its clinical phenotype to the identification of its neuropathological features, neurochemical processes and genetic factors. PD pathophysiology can be abstracted at many levels, including molecular pathogenesis, cellular abnormalities, neurochemical variations, site and circuit dysfunction, and dysfunction of the network. With the tremendous advancements in our understanding of these processes it is evident that an ever-expanding wealth of information will continue to emerge and contribute to the development of better treatment approaches for the management of PD. This chapter aims to discuss primarily the neurochemical changes occurring in PD, highlighting the various neurotransmitters involved in the pathophysiology of the disease, along with their receptors and actions. The chapter also covers the dopaminergic and non-dopaminergic pathways involved and how their imbalance contributes to the occurrence of the disease symptoms. Furthermore, the chapter gives an insight into the latest developments and challenges in the treatment of PD.
