Parkinson Disease

Homayoun, Houman

doi:10.7326/aitc201809040

Cited by 77 publications

(68 citation statements)

References 55 publications

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“…Analysis of the main LD effect showed that ReHo values increased in the left putamen and decreased in the left caudate nucleus after taking antiparkinsonian drugs, including LD. LD, the precursor to dopamine, is the most effective medication to improve motor symptoms in PD patients 10 . Dopamine has a role in modulating firing of medium spiny neurons in the striatum, including the putamen and caudate nucleus 11 , 12 .…”

Section: Discussionmentioning

confidence: 99%

Dysfunction in superior frontal gyrus associated with diphasic dyskinesia in Parkinson’s disease

Shen

Yuan

Wang

et al. 2020

npj Parkinsons Dis.

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Alterations in brain function in Parkinson’s disease (PD) patients with diphasic dyskinesia have not been investigated. We aimed to explore the alterations in regional brain function. Each of 53 levodopa (LD)-treated PD patients had two resting-state functional magnetic resonance imaging (rs-fMRI) scans in the same morning, before and after taking LD. The regional homogeneity (ReHo) approach was used to reveal local synchronization changes. Two-way factorial repeated measures analysis of covariance, with group as a between-subject factor and LD effect as a within-subject factor, was performed to explore the two main effects and interaction. Interactive analysis was used to show outcomes that combined disease status and LD effect. Spearman’s correlations were used to detect associations between interactive brain regions and severity of dyskinetic symptoms, assessed by the Unified Dyskinesia Rating Scale (UDyRS) scores, along with moderation analyses. There was no significant difference in the main group effect analysis. Significantly different clusters obtained from main LD effect analysis were in left caudate nucleus and putamen. ReHo values decreased in the caudate nucleus and increased in the putamen during the ON state after taking LD. Interaction between group and LD effect was found in left medial superior frontal gyrus (mSFG), where there were the lowest ReHo values, and was negatively correlated with UDyRS scores in the diphasic dyskinetic group during the ON state. The relationship was independent of LD dose. Abnormal local synchronization in the mSFG is closely associated with the development of diphasic dyskinesia in PD patients.

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Section: Discussionmentioning

confidence: 99%

Dysfunction in superior frontal gyrus associated with diphasic dyskinesia in Parkinson’s disease

Shen

Yuan

Wang

et al. 2020

npj Parkinsons Dis.

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“…Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease (AD), and affects approximately 2-3% of the world's population over the age of 65 [1,2]. Although the etiology and pathogenic mechanism of PD are not fully understood, a variety of genetic factors and environmental exposures have been identi ed to contribute to the pathological progression of PD, and the possible mechanisms include the changes in dopamine metabolism, mitochondrial dysfunction, endoplasmic reticulum stress, impaired autophagy and deregulated immunity [3].…”

Section: Read Full Licensementioning

confidence: 99%

Opposing functions of β-arrestin 1 and 2 in Parkinson’s disease via microglia inflammation and Nprl3

Fang

Jiang

et al. 2020

Preprint

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Background Although β-arrestins (ARRBs) regulate diverse physiological and pathophysiological processes, their function and regulation in Parkinson’s disease (PD) remain poorly defined. Methods We measured expression of ARRB1 and ARRB2 in liposaccharide (LPS)-induced and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. ARRB1-deficient and ARRB2-deficient mouse were used to assess the impact of ARRBs on dopaminergic (DA) neuron loss and microglia activation in PD mouse models. After primary mouse DA neurons were exposed to the conditioned medium from ARRB1 knockdown or ARRB2 knockout microglia stimulated by LPS plus interferon γ (IFN-γ), the degeneration of DA neurons was quantified. Gain- and loss-of-function studies were used to study the effects of ARRBs on microglia activation in vitro. To further understand the mechanism, we measured the activation of classical inflammatory pathways and used RNA sequencing to identify the novel downstream effector of ARRBs. Result In this study, we demonstrate that expression of ARRB1 and ARRB2, particularly in microglia, is reciprocally regulated in PD mouse models. ARRB1 ablation ameliorates, whereas ARRB2 knockout aggravates, the pathological features of PD, including DA neuron loss, neuroinflammation and microglia activation in vivo, as well as microglia-mediated neuron damage and inflammation in vitro. In parallel, ARRB1 and ARRB2 produce adverse effects on the activation of inflammatory signal transducers and activators of transcription 1 (STAT1) and nuclear factor-κB (NF-κB) pathways in microglia. We also show that two ARRBs competitively interact with activated p65 in the NF-κB pathway and that nitrogen permease regulator-like 3 (Nprl3), a functionally poorly characterized protein, is a novel effector acting downstream of both ARRBs. Conclusion Collectively, these data demonstrate that two closely related ARRBs have completely opposite functions in microglia-mediated inflammatory responses, via Nprl3, and differentially affect the pathogenesis of PD, and suggest a potential therapeutic strategy.

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“…In this way, PD generates a series of clinical symptoms, classified as motor symptoms and nonmotor symptoms. Resting tremor, bradykinesia, and rigidity are defined as classical parkinsonian motor symptoms, which usually develop unilaterally and later spread to the contralateral side, but ordinarily remain asymmetrical throughout the disease course ( 4 , 5 ). Nonmotor symptoms include hyposmia, cognitive disorder, sleep disorder, autonomic dysfunction, and psychiatric symptoms ( 4 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

“…Resting tremor, bradykinesia, and rigidity are defined as classical parkinsonian motor symptoms, which usually develop unilaterally and later spread to the contralateral side, but ordinarily remain asymmetrical throughout the disease course ( 4 , 5 ). Nonmotor symptoms include hyposmia, cognitive disorder, sleep disorder, autonomic dysfunction, and psychiatric symptoms ( 4 , 5 ). To diagnose PD, not only are the mandatory criteria needed but also diagnostic exclusion criteria and red flags for PD diagnosis should be considered ( 4 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

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A Han Chinese Family With Early-Onset Parkinson's Disease Carrying Novel Frameshift Mutation and Compound Heterozygous Mutation of PRKN Appearing Incompatible With MDS Clinical Diagnostic Criteria

et al. 2020

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Around 15% of patients with Parkinson's disease (PD) have a family history, and 5–10% have confirmed genetic causes. PRKN is the most common gene responsible for early-onset Parkinson's disease (EOPD), while rare variants of PLA2G6 likely raise PD susceptibility in the Chinese population. We investigated the genetic information of 13 members of a Han Chinese family with known EOPD by whole-exome sequencing and Sanger sequencing, and analyzed the clinical history, physical examination, blood laboratory test, and brain imaging data of the patients. Two members, including the proband, were suspected of having EOPD. A novel homozygous frameshift mutation, c.856delT, and a compound heterozygous mutation, c.1321T>C/c.856delT of PRKN , were identified, as well as two single nucleotide variants of PLA2G6 and TENM4 . The proband exhibited a rare symmetrical resting tremor limited to her lower limbs and never exhibited signs of rigidity. 18 F-DOPA PET/CT scan indicated a symmetrical reduced signaling in the striatum. The novel frameshift mutation and compound heterozygous mutation of PRKN are likely to be the genetic causes of EOPD in this family.

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Parkinson Disease

Cited by 77 publications

References 55 publications

Dysfunction in superior frontal gyrus associated with diphasic dyskinesia in Parkinson’s disease

Dysfunction in superior frontal gyrus associated with diphasic dyskinesia in Parkinson’s disease

Opposing functions of β-arrestin 1 and 2 in Parkinson’s disease via microglia inflammation and Nprl3

A Han Chinese Family With Early-Onset Parkinson's Disease Carrying Novel Frameshift Mutation and Compound Heterozygous Mutation of PRKN Appearing Incompatible With MDS Clinical Diagnostic Criteria

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