The serotonergic system in Parkinson’s patients with dyskinesia: evidence from imaging studies

Pagano, Gennaro; Niccolini, Flavia; Politis, Marios

doi:10.1007/s00702-017-1823-7

Cited by 27 publications

(12 citation statements)

References 45 publications

(85 reference statements)

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“…MRI studies examining cortical thickness and subcortical nuclei volume have linked both fatigue and somnolence to thalamic atrophy as well [62]. There may also be susceptibility to levodopa-induced dyskinesias [63]. This subgroup needs specific personalized strategies, including:…”

Section: Nonmotor Subtypesmentioning

confidence: 99%

Therapy of Parkinson's Disease Subtypes

et al. 2020

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Early descriptions of subtypes of Parkinson's disease (PD) are dominated by the approach of predetermined groups. Experts defined, from clinical observation, groups based on clinical or demographic features that appeared to divide PD into clinically distinct subsets. Common bases on which to define subtypes have been motor phenotype (tremor dominant vs akinetic-rigid or postural instability gait disorder types), age, nonmotor dominant symptoms, and genetic forms. Recently, data-driven approaches have been used to define PD subtypes, taking an unbiased statistical approach to the identification of PD subgroups. The vast majority of data-driven subtyping has been done based on clinical features. Biomarker-based subtyping is an emerging but still quite undeveloped field. Not all of the subtyping methods have established therapeutic implications. This may not be surprising given that they were born largely from clinical observations of phenotype and not in observations regarding treatment response or biological hypotheses. The next frontier for subtypes research as it applies to personalized medicine in PD is the development of genotype-specific therapies. Therapies for GBA-PD and LRRK2-PD are already under development. This review discusses each of the major subtyping systems/methods in terms of its applicability to therapy in PD, and the opportunities and challenges designing clinical trials to develop the evidence base for personalized medicine based on subtypes.

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Section: Nonmotor Subtypesmentioning

confidence: 99%

Therapy of Parkinson's Disease Subtypes

et al. 2020

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“…Network impairment in such neurodegenerative disorders has been selectively associated with neurological symptoms such as cognitive, motor, Electronic supplementary material The online version of this article (https ://doi.org/10.1007/s0041 5-020-09806 -3) contains supplementary material, which is available to authorized users. and non-motor symptoms [4][5][6][7][8]. Tools to measure impaired neurotransmitter networks integrity require either the application of PET or complex MRI methodology with contrast injection.…”

Section: Introductionmentioning

confidence: 99%

Impaired connectivity within neuromodulatory networks in multiple sclerosis and clinical implications

et al. 2020

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There is mounting evidence regarding the role of impairment in neuromodulatory networks for neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease. However, the role of neuromodulatory networks in multiple sclerosis (MS) has not been assessed. We applied resting-state functional connectivity and graph theory to investigate the changes in the functional connectivity within neuromodulatory networks including the serotonergic, noradrenergic, cholinergic, and dopaminergic systems in MS. Twenty-nine MS patients and twenty-four age- and gender-matched healthy controls performed clinical and cognitive assessments including the expanded disability status score, symbol digit modalities test, and Hamilton Depression rating scale. We demonstrated a diffuse reorganization of network topography (P < 0.01) in serotonergic, cholinergic, noradrenergic, and dopaminergic networks in patients with MS. Serotonergic, noradrenergic, and cholinergic network functional connectivity derangement was associated with disease duration, EDSS, and depressive symptoms (P < 0.01). Derangements in serotonergic, noradrenergic, cholinergic, and dopaminergic network impairment were associated with cognitive abilities (P < 0.01). Our results indicate that functional connectivity changes within neuromodulatory networks might be a useful tool in predicting disability burden over time, and could serve as a surrogate endpoint to assess efficacy for symptomatic treatments.

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“…A study has suggested the degeneration of serotonergic terminals is an early process in the pathogenesis of PD and with preferential lower rate of degeneration as compare of dopaminergic neurons [59]. The aberrant spread of serotonergic terminals in putamen, non-physiologically converts the exogenous levodopa and results into higher swings of dopamine that develops the levodopa associated dyskinesia [60]. The cholinergic and dopaminergic neurons are highly conserved in the striatum and extensively interact bidirectionally to regulate the motor coordination, cognitive function and rewards [61].…”

Section: Discussionmentioning

confidence: 99%

Systems pharmacology based approach to investigate the in-vivo therapeutic efficacy of Albizia lebbeck (L.) in experimental model of Parkinson’s disease

Saleem

Raza

Anwar

et al. 2019

BMC Complement Altern Med

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BackgroundParkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons in substantia nigra pars compacta and clinically manifested mainly with motor dysfunctions. Plants are rich source of medicinally important bioactive compounds and inhabitants of underdeveloped countries used plants for treatment of various ailments. Albizia lebbeck has been reported to possess antioxidant and neuroprotective properties that suggest the evaluation of its traditional therapeutic potential in neurodegenerative diseases.The aim of present study was to validate the traditional use of Albizia lebbeck (L.) and delineate its mechanism of action in PD. The systems pharmacology approach was employed to explain the Albizia lebbeck (L.) mechanism of action in PD.MethodsThe haloperidol-induced catalepsy was adopted as experimental model of PD for in-vivo studies in wistar albino rats. The systems pharmacology approach was employed to explain the Albizia lebbeck (L.) mechanism of action in PD.ResultsIn-vivo studies revealed that Albizia lebbeck improved the motor functions and endurance as demonstrated in behavioral studies which were further supported by the rescue of endogenous antioxidant defense and reversal of ultrastructural damages in histological studies. System pharmacology approach identified 25 drug like compounds interacting with 132 targets in a bipartite graph that revealed the synergistic mechanism of action at system level. Kaemferol, phytosterol and okanin were found to be the important compounds nodes with prominent target nodes of TDP1 and MAPT.ConclusionThe therapeutic efficiency of Albizia lebbeck in PD was effectively delineated in our experimental and systems pharmacology approach. Moreover, this approach further facilitates the drug discovery from Albizia lebbeck for PD.

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The serotonergic system in Parkinson’s patients with dyskinesia: evidence from imaging studies

Cited by 27 publications

References 45 publications

Therapy of Parkinson's Disease Subtypes

Therapy of Parkinson's Disease Subtypes

Impaired connectivity within neuromodulatory networks in multiple sclerosis and clinical implications

Systems pharmacology based approach to investigate the in-vivo therapeutic efficacy of Albizia lebbeck (L.) in experimental model of Parkinson’s disease

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