NMDA antagonists for treating the non-motor symptoms in Parkinson’s disease

Vanle, Brigitte; Olcott, William; Jimenez, Jaime M; Bashmi, Luma; Danovitch, Itai; IsHak, Waguih William

doi:10.1038/s41398-018-0162-2

Cited by 57 publications

(38 citation statements)

References 78 publications

(118 reference statements)

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“…Therefore, future investigations should consider the balance between receptor-related pro-death and pro-survival effects. In addition, traditional treatment mainly focuses on the improvement of motor dysfunction and ignores non-motor symptoms in PD, such as anxiety, apathy, cognitive dysfunction, and depression [119].…”

Section: Discussionmentioning

confidence: 99%

Roles of Glutamate Receptors in Parkinson’s Disease

Zhang

et al. 2019

IJMS

119

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Parkinson’s disease is a progressive neurodegenerative disorder resulting from the degeneration of pigmented dopaminergic neurons in the substantia nigra pars compacta. It induces a series of functional modifications in the circuitry of the basal ganglia nuclei and leads to severe motor disturbances. The amino acid glutamate, as an excitatory neurotransmitter, plays a key role in the disruption of normal basal ganglia function regulated through the interaction with its receptor proteins. It has been proven that glutamate receptors participate in the modulation of neuronal excitability, transmitter release, and long-term synaptic plasticity, in addition to being related to the altered neurotransmission in Parkinson’s disease. Therefore, they are considered new targets for improving the therapeutic strategies used to treat Parkinson’s disease. In this review, we discuss the biological characteristics of these receptors and demonstrate the receptor-mediated neuroprotection in Parkinson’s disease. Pharmacological manipulation of these receptors during anti-Parkinsonian processes in both experimental studies and clinical trials are also summarized.

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Section: Discussionmentioning

confidence: 99%

Roles of Glutamate Receptors in Parkinson’s Disease

Zhang

et al. 2019

IJMS

119

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“…As in major depression, selective serotonin reuptake inhibitors, tricyclic antidepressants, serotonin and NA reuptake inhibitors, and monoamine oxidase inhibitors are used in the pharmacotherapy, with partial effect, probably influenced by the neurodegeneration of the serotonergic and noradrenergic systems (Ryan et al, 2019). The use of antidepressant that do not target monoaminergic systems may potentially offer benefit in these patients (Vanle et al, 2018).…”

Section: Depressionmentioning

confidence: 99%

The Noradrenergic System in Parkinson’s Disease

et al. 2020

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Nowadays it is well accepted that in Parkinson's disease (PD), the neurodegenerative process occurs in stages and that damage to other areas precedes the neuronal loss in the substantia nigra pars compacta, which is considered a pathophysiological hallmark of PD. This heterogeneous and progressive neurodegeneration may explain the diverse symptomatology of the disease, including motor and non-motor alterations. In PD, one of the first areas undergoing degeneration is the locus coeruleus (LC). This noradrenergic nucleus provides extensive innervation throughout the brain and plays a fundamental neuromodulator role, participating in stress responses, emotional memory, and control of motor, sensory, and autonomic functions. Early in the disease, LC neurons suffer modifications that can condition the effectiveness of pharmacological treatments, and importantly, can lead to the appearance of common non-motor symptomatology. The noradrenergic system also exerts anti-inflammatory and neuroprotective effect on the dopaminergic degeneration and noradrenergic damage can consequently condition the progress of the disease. From the pharmacological point of view, it is also important to understand how the noradrenergic system performs in PD, since noradrenergic medication is often used in these patients, and drug interactions can take place when combining them with the gold standard drug therapy in PD, L-3,4-dihydroxyphenylalanine (L-DOPA). This review provides an overview about the functional status of the noradrenergic system in PD and its contribution to the efficacy of pharmacologicalbased treatments. Based on preclinical and clinical publications, a special attention will be dedicated to the most prevalent non-motor symptoms of the disease.

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“…NMDA receptors play an essential role in synaptic plasticity and synaptogenesis (Nicoll and Malenka, 1999 ). Dysregulation of NMDA receptors activity is associated with cognitive impairment in AD (Avila et al, 2017 ), PD (Vanle et al, 2018 ), and HD (Giralt et al, 2012 ) among others. Because their function is regulated by different cell modifications, the effect of PAC1R signaling on NMDA receptors activity has been studied.…”

Section: Mechanisms Of Action: From Receptor (Pac1 Vpac1 and Vpac2) mentioning

confidence: 99%