Toward neuroprotective treatments of Parkinson’s disease

Kim, Kwangsoo

doi:10.1073/pnas.1703362114

Cited by 22 publications

(13 citation statements)

References 20 publications

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“…All these signify the importance of age as a nonmodifiable risk factor of PI in PD. Moreover, age establishes a new role for neuroprotective agents as a possible therapeutic agent in PD patients [59,60].…”

Section: Factors Contributing To Pi In Parkinson’s Diseasementioning

confidence: 99%

Postural Instability in Parkinson’s Disease: A Review

Palakurthi

Burugupally

2019

Brain Sciences

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Parkinson’s disease (PD) is a heterogeneous progressive neurodegenerative disorder, which typically affects older adults; it is predicted that by 2030 about 3% of the world population above 65 years of age is likely to be affected. At present, the diagnosis of PD is clinical, subjective, nonspecific, and often inadequate. There is a need to quantify the PD factors for an objective disease assessment. Among the various factors, postural instability (PI) is unresponsive to the existing treatment strategies resulting in morbidity. In this work, we review the physiology and pathophysiology of postural balance that is essential to treat PI among PD patients. Specifically, we discuss some of the reported factors for an early PI diagnosis, including age, nervous system lesions, genetic mutations, abnormal proprioception, impaired reflexes, and altered biomechanics. Though the contributing factors to PI have been identified, how their quantification to grade PI severity in a patient can help in treatment is not fully understood. By contextualizing the contributing factors, we aim to assist the future research efforts that underpin posturographical and histopathological studies to measure PI in PD. Once the pathology of PI is established, effective diagnostic tools and treatment strategies could be developed to curtail patient falls.

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Section: Factors Contributing To Pi In Parkinson’s Diseasementioning

confidence: 99%

Postural Instability in Parkinson’s Disease: A Review

Palakurthi

Burugupally

2019

Brain Sciences

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“…Since its introduction in the 1960 s, levodopa has been the gold-standard choice for treatment of PD-related motor symptoms, such as slowness of movement, rigidity and tremor [4]. Levodopa loses efficacy over time and prolonged use is accompanied by motor complications including refractory motor fluctuations and dyskinesia, which are observed in almost all patients with PD after 4–6 years [5–9]. Despite the availability of other symptomatic treatments such as dopamine agonists, monoamine oxidase type B inhibitors (MAO-Bi) and amantadine—used instead of, or in combination with, levodopa in order to optimize symptomatic control—an unmet medical need still remains, as no treatments with a direct effect on the underlying disease pathophysiology are currently available and the disease continues to progress regardless of symptomatic therapy [5, 10, 11].…”

Section: Introductionmentioning

confidence: 99%

Treatment Patterns in Patients with Incident Parkinson’s Disease in the United States

Houghton

Boess

Verselis

et al. 2019

JPD

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Background:Treatment patterns in Parkinson’s disease (PD) have not been extensively studied for nearly two decades. Insurance claims are appropriate for such analysis.Objective:To understand the standard of care use of symptomatic treatments in new cases of PD and factors associated with treatment choice.Methods:Retrospective cohort study using claims data from the United States between 2008 and 2016. We used Kaplan–Meier methodology to estimate time to treatment start and switch or add-on therapy and Cox proportional hazards models to identify predictors.Results:We identified 68,532 patients eligible for treatment pattern analyses. Median time from diagnosis until first treatment was 37 days (95% confidence interval: 36–38). Two distinct patterns of treatment initiation were identified: fast initiators and patients with delayed treatment start (or no recorded treatment). Levodopa therapies were the most commonly prescribed treatment class (52.6%). Increased age was associated with shorter time to start of treatment with levodopa. Younger age was associated with shorter time to initiation of dopamine agonists and other symptomatic treatments. Patients that initiated treatment with levodopa/combinations had the fewest switches/add-ons [30.4%; median time 7.29 (6.71, 8.13) years]. Older patients had fewer switch/add-on therapies, but only in the group that started with levodopa/combination therapy.Conclusions:Time from diagnosis to treatment start was relatively short, suggesting that PD diagnosis, as reflected in the database, is closely linked to start of symptomatic treatment. Levodopa treatment remains the most common treatment, especially for older patients. Delayed treatment start was associated with increased age and comorbidity.

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“…Although the exact mechanisms of AD pathogenesis are unclear, intracellular and extracellular Aβ are thought to be major causative factors associated with AD-related pathologies, such as neurodegeneration and cognitive dysfunction [45][46][47]. Interestingly, Nurr1 is known to act as a critical regulator of hippocampal function, hippocampal synaptic plasticity, and cognitive functions [15,[48][49][50][51][52][53][54][55], and is an essential mediator of neuroprotection or anti-inflammation after exposure to neuropathological stress [19,[56][57][58][59][60][61]. In addition, a number of studies have indicated altered levels of Nurr1 in Aβ-treated neuronal cells, animal models of AD, and the brains of patients with AD [13,[62][63][64][65], implying that Nurr1 may play a role in the pathogenesis of AD.…”

Section: The Roles Of Nurr1 In Ad-related Pathologymentioning

confidence: 99%

The Critical Role of Nurr1 as a Mediator and Therapeutic Target in Alzheimer’s Disease-related Pathogenesis

et al. 2020

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Several studies have revealed that the transcription factor nuclear receptor related 1 (Nurr1) plays several roles not only in the regulation of gene expression related to dopamine synthesis, but also in alternative splicing, and miRNA targeting. Moreover, it regulates cognitive functions and protects against inflammationinduced neuronal death. In particular, the role of Nurr1 in the pathogenesis of Parkinson's disease (PD) has been well investigated; for example, it has been shown that it restores behavioral and histological impairments in PD models. Although many studies have evaluated the connection between Nurr1 and PD pathogenesis, the role of Nurr1 in Alzheimer's disease (AD) remain to be studied. There have been several studies describing Nurr1 protein expression in the AD brain. However, only a few studies have examined the role of Nurr1 in the context of AD. Therefore, in this review, we highlight the overall effects of Nurr1 under the neuropathologic conditions related to AD. Furthermore, we suggest the possibility of using Nurr1 as a therapeutic target for AD or other neurodegenerative disorders.

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Toward neuroprotective treatments of Parkinson’s disease

Cited by 22 publications

References 20 publications

Postural Instability in Parkinson’s Disease: A Review

Postural Instability in Parkinson’s Disease: A Review

Treatment Patterns in Patients with Incident Parkinson’s Disease in the United States

The Critical Role of Nurr1 as a Mediator and Therapeutic Target in Alzheimer’s Disease-related Pathogenesis

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