About this Research Topic
Dopaminergic neurodegeneration from the mesencephalon has been the hallmark and main anatomopathological hypothesis of Parkinson’s disease (PD) for almost 70 years, and dopamine replacement therapy still remains the best symptomatic treatment to improve quality of life of parkinsonian patients. The interest brought to non-dopaminergic systems in PD is not new, neither in the process of the disease nor in the benefit/side effects of the therapies. Indeed, PD cannot be considered as a pure motor disease and understood only through the prism of the nigrostriatal dopaminergic pathway deficiency. Moreover, the disease progresses through different stages and damage to other areas and neurochemical systems precede the degeneration of dopaminergic neurons. In particular, those systems affected in the so-called prodromal or presymptomatic phases contribute to the malfunctioning of the motor circuits and also sustain the appearance of the non-motor component of the disease. The non-motor symptoms are increasingly recognized in PD and severely alter the quality of life of the patients, since they are often more debilitating than the motor ones and rarely respond to dopatherapy. Moreover, the studies addressing the mechanisms of action of antiparkinsonian drugs have revealed that their benefits/side effects involved mechanisms other than the dopaminergic ones.
PD is therefore a complex neurological disorder with prodromal, symptomatic and iatrogenic phases, during which each patient exhibits its own denervation and clinical profiles. While dopatherapy plays a key role in counteracting motor symptoms, it clearly fails to address the wide myriad of non-motor symptoms that can appear years before motor symptoms onset. Among others, we can cite olfactory dysfunction, gastrointestinal disturbances, REM sleep behavior disorders, psychiatric disorders and cognitive deficits. Even for dementia, which is the worst evolution of the disease, the therapeutic approach remains elusive. Many of these non-motor symptoms are under-estimated, untreated (lack of access to this prodromal phase), and often masked with the motor symptomatology.
A better understanding of the pharmacology and the involvement of non-dopaminergic systems in PD is an essential step to better apprehend patients’ treatment. In addition to the glutamatergic and GABAergic executive systems, other neurochemical systems have been the object of a special pharmacological attention including noradrenergic, serotonergic and cholinergic systems. Other pathways such as adenosine, histamine and opioids need to be deeply explored as well. More generally, the molecular and cellular events in the disease with special inference to Lewy bodies and oxidative metabolism disturbances point to widespread alterations of neurotransmitter systems as well as altered interactions between neurons and glia.
The purpose of this Research Topic is to collect information on the role of non-dopaminergic systems in PD and the possible pharmacological targets to treat this disease regardless of its stage. Together with clinical data, pre-clinical studies obtained in animal models of the disease will be highly considered. Indeed, while none of the animal models available resume the human disease, most of them permit to focus in a neuropharmacological approach on identified lesions and associated group of symptoms, target cellular or molecular aspects of the pathophysiology, and/or address specific stage of the disease.
Keywords: Motor and non-motor symptoms, metabolism, neuromodulation, pathophysiology, therapy
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