The Future of Research in Parkinson Disease

Jankovic, Joseph; Sherer, Todd

doi:10.1001/jamaneurol.2014.1717

Cited by 31 publications

(23 citation statements)

References 8 publications

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“…Symptoms of PD appear most often around the age of 60 [1,2]. Although the cause of the disease is still unknown, remarkable progress has been made to understand the underlying mechanisms [3]. Several genes, such as α-synuclein, parkin, PINK1 (phosphatase and tensin homologue-induced kinase 1), DJ1 (also known as Parkinson disease protein 7, PARK7 gene); and also environmental factors, like physical trauma, infections, and toxic effects have been identified to have a role in PD [4,5].…”

Section: Introductionmentioning

confidence: 99%

Effects of Postnatal Enriched Environment in a Model of Parkinson’s Disease in Adult Rats

Jungling

Reglődi

Karadi

et al. 2017

IJMS

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Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson’s disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life.

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Section: Introductionmentioning

confidence: 99%

Effects of Postnatal Enriched Environment in a Model of Parkinson’s Disease in Adult Rats

Jungling

Reglődi

Karadi

et al. 2017

IJMS

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“…PD is characterized by the presence of Lewy bodies that are primarily made by α-synuclein, and by the loss of dopaminergic neurons in the substantia nigra [47]. The most common symptoms of PD are bradykinesia, tremor, rigidity, and postural instability [48]. Unfortunately, when these signs appear, there is a loss of more than half of nigrostriatal dopaminergic terminals [48].…”

Section: Pdmentioning

confidence: 99%

“…The most common symptoms of PD are bradykinesia, tremor, rigidity, and postural instability [48]. Unfortunately, when these signs appear, there is a loss of more than half of nigrostriatal dopaminergic terminals [48]. Hence, the discovery of diagnostic biomarkers that may select individuals at risk to develop PD would be of great relevance [48].…”

Section: Pdmentioning

confidence: 99%

“…Unfortunately, when these signs appear, there is a loss of more than half of nigrostriatal dopaminergic terminals [48]. Hence, the discovery of diagnostic biomarkers that may select individuals at risk to develop PD would be of great relevance [48]. There are different PD subtypes and, besides the characteristic motor symptoms, there are a large variety of other symptoms, including psychiatric and cognitive dysfunctions [48].…”

Section: Pdmentioning

confidence: 99%

“…Hence, the discovery of diagnostic biomarkers that may select individuals at risk to develop PD would be of great relevance [48]. There are different PD subtypes and, besides the characteristic motor symptoms, there are a large variety of other symptoms, including psychiatric and cognitive dysfunctions [48]. Moreover, nonmotor symptoms, such as dysautonomia, hyposmia, rapid eye movement, and sleep disorders, could anticipate motor symptoms [48].…”

Section: Pdmentioning

confidence: 99%

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The Dichotomic Role of Macrophage Migration Inhibitory Factor in Neurodegeneration

Basile

Battaglia

Bruno

et al. 2020

IJMS

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Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine expressed by different cell types and exerting multiple biological functions. It has been shown that MIF may be involved in several disorders, including neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Parkinson disease (PD), and Huntington disease (HD), that represent an unmet medical need. Therefore, further studies are needed to identify novel pathogenetic mechanisms that may translate into tailored therapeutic approaches so to improve patients’ survival and quality of life. Here, we reviewed the preclinical and clinical studies investigating the role of MIF in ALS, PD, and HD. The emerging results suggest that MIF might play a dichotomic role in these disorders, exerting a protective action in ALS, a pathogenetic action in HD, and a yet undefined and debated role in PD. The better understanding of the role of MIF in these diseases could allow its use as a novel diagnostic and therapeutic tool for the monitoring and treatment of the patients and for eventual biomarker-driven therapeutic approaches.

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Estimating personalized diagnostic rules depending on individualized characteristics

Liu

Wang

Huang

et al. 2016

Statistics in Medicine

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There is an increasing demand for personalization of disease screening based on assessment of patient risk and other characteristics. For example, in breast cancer screening, advanced imaging technologies have made it possible to move away from “one-size-fits-all” screening guidelines to targeted risk-based screening for those who are in need. Since diagnostic performance of various imaging modalities may vary across subjects, applying the most accurate modality to the patients who would benefit the most requires personalized strategy. To address these needs, we propose novel machine learning methods to estimate personalized diagnostic rules for medical screening or diagnosis by maximizing a weighted combination of sensitivity and specificity across subgroups of subjects. We first develop methods that can be applied when competing modalities or screening strategies are observed on the same subject (paired design). Next, we present methods for studies where not all subjects receive both modalities (unpaired design). We study theoretical properties including consistency and risk bound of the personalized diagnostic rules, and conduct simulation studies to examine performance of the proposed methods. Lastly, we analyze data collected from a brain imaging study of Parkinson’s disease using positron emission tomography (PET) and diffusion tensor imaging (DTI) with paired and unpaired designs. Our results show that in some cases a personalized modality assignment is estimated to improve empirical AUC compared to a “one-size-fits-all” assignment strategy.

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The Future of Research in Parkinson Disease

Cited by 31 publications

References 8 publications

Effects of Postnatal Enriched Environment in a Model of Parkinson’s Disease in Adult Rats

Effects of Postnatal Enriched Environment in a Model of Parkinson’s Disease in Adult Rats

The Dichotomic Role of Macrophage Migration Inhibitory Factor in Neurodegeneration

Estimating personalized diagnostic rules depending on individualized characteristics

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