Levodopa-Induced Dyskinesias in Parkinson’s Disease: An Overview on Pathophysiology, Clinical Manifestations, Therapy Management Strategies and Future Directions

Biase, Lazzaro di; Pecoraro, Pasquale Maria; Carbone, Simona Paola; Caminiti, Maria Letizia; Lazzaro, Vincenzo Di

doi:10.3390/jcm12134427

Cited by 19 publications

(6 citation statements)

References 320 publications

(487 reference statements)

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“…DA replacement via L-dopa (L-3,4-dihydroxyphenylalanine), which is a DA precursor, is the most common treatment. However, not only the efficacy of this drug is invariably reduced in a few years, but long-term treatment may cause severe dyskinesia or involuntary movements [ 3 , 25 , 28 , 29 ]. Hence, extensive efforts to find novel therapies are ongoing.…”

Section: Pd Pathophysiology and Current Treatmentsmentioning

confidence: 99%

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

Soares,

Costa,

Ferrolho

et al. 2024

Cells

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Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by resting tremor, bradykinesia, rigidity, and postural instability that also includes non-motor symptoms such as mood dysregulation. Dopamine (DA) is the primary neurotransmitter involved in this disease, but cholinergic imbalance has also been implicated. Current intervention in PD is focused on replenishing central DA, which provides remarkable temporary symptomatic relief but does not address neuronal loss and the progression of the disease. It has been well established that neuronal nicotinic cholinergic receptors (nAChRs) can regulate DA release and that nicotine itself may have neuroprotective effects. Recent studies identified nAChRs in nonneuronal cell types, including glial cells, where they may regulate inflammatory responses. Given the crucial role of neuroinflammation in dopaminergic degeneration and the involvement of microglia and astrocytes in this response, glial nAChRs may provide a novel therapeutic target in the prevention and/or treatment of PD. In this review, following a brief discussion of PD, we focus on the role of glial cells and, specifically, their nAChRs in PD pathology and/or treatment.

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Section: Pd Pathophysiology and Current Treatmentsmentioning

confidence: 99%

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

Soares,

Costa,

Ferrolho

et al. 2024

Cells

View full text Add to dashboard Cite

show abstract

“…DA replacement via L-dopa (L-3,4-dihydroxyphenylalanine), which is DA precursor, is the most common treatment. However, not only the efficacy of this drug is invariably reduced in a few years, but long-term treatment may cause severe dyskinesia or involuntary movements [3,25,28,29]. Hence, extensive efforts to find novel therapies are ongoing.…”

Section: Pd Pathophysiology and Current Treatmentsmentioning

confidence: 99%

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

Soares,

Costa,

Ferrolho

et al. 2024

Preprint

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Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by resting tremor, bradykinesia, rigidity, postural instability, that also includes non-motor symptoms such as mood dysregulation. Dopamine (DA) is the primary neurotransmitter involved in this disease, but cholinergic imbalance has also been implicated. Current intervention in PD is focused on replenishing central DA, which provides remarkable temporary symptomatic relief but does not address the neuronal loss and the progression of the disease. It has been well established that neuronal nicotinic cholinergic receptors (nAChRs) can regulate DA release and that nicotine itself may have neuroprotective effects. Recent studies have identified nAChRs in nonneuronal cell types including glial cells, where they may regulate inflammatory responses. Given the crucial role of neuroinflammation in dopaminergic degeneration, and the involvement of microglia and astrocytes in this response, glial nAChRs may provide a novel therapeutic target in prevention and/or treatment of PD. In this review, following a brief discussion of PD, we focus on the role of glial cells and specifically their nAChRs in PD pathology and/or treatment.

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“…This involves the interaction between the supplementary motor area and the basal ganglia, which are crucial for movement preparation [176,255,278,279]. DBS-induced reductions in medication dosages, which in turn diminish medication-related side effects such as troublesome dyskinesia, might be another major factor facilitating synergistic effects [209,210,230,280].…”

Section: Gaitmentioning

confidence: 99%

Does Impaired Plantar Cutaneous Vibration Perception Contribute to Axial Motor Symptoms in Parkinson’s Disease? Effects of Medication and Subthalamic Nucleus Deep Brain Stimulation

Heß,

Themann,

Oehlwein

et al. 2023

Brain Sciences

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Objective: To investigate whether impaired plantar cutaneous vibration perception contributes to axial motor symptoms in Parkinson’s disease (PD) and whether anti-parkinsonian medication and subthalamic nucleus deep brain stimulation (STN-DBS) show different effects. Methods: Three groups were evaluated: PD patients in the medication “on” state (PD-MED), PD patients in the medication “on” state and additionally “on” STN-DBS (PD-MED–DBS), as well as healthy subjects (HS) as reference. Motor performance was analyzed using a pressure distribution platform. Plantar cutaneous vibration perception thresholds (VPT) were investigated using a customized vibration exciter at 30 Hz. Results: Motor performance of PD-MED and PD-MED–DBS was characterized by greater postural sway, smaller limits of stability ranges, and slower gait due to shorter strides, fewer steps per minute, and broader stride widths compared to HS. Comparing patient groups, PD-MED–DBS showed better overall motor performance than PD-MED, particularly for the functional limits of stability and gait. VPTs were significantly higher for PD-MED compared to those of HS, which suggests impaired plantar cutaneous vibration perception in PD. However, PD-MED–DBS showed less impaired cutaneous vibration perception than PD-MED. Conclusions: PD patients suffer from poor motor performance compared to healthy subjects. Anti-parkinsonian medication in tandem with STN-DBS seems to be superior for normalizing axial motor symptoms compared to medication alone. Plantar cutaneous vibration perception is impaired in PD patients, whereas anti-parkinsonian medication together with STN-DBS is superior for normalizing tactile cutaneous perception compared to medication alone. Consequently, based on our results and the findings of the literature, impaired plantar cutaneous vibration perception might contribute to axial motor symptoms in PD.

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Levodopa-Induced Dyskinesias in Parkinson’s Disease: An Overview on Pathophysiology, Clinical Manifestations, Therapy Management Strategies and Future Directions

Cited by 19 publications

References 320 publications

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

Does Impaired Plantar Cutaneous Vibration Perception Contribute to Axial Motor Symptoms in Parkinson’s Disease? Effects of Medication and Subthalamic Nucleus Deep Brain Stimulation

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