scholarly journals Cyclin-G-associated kinase GAK/Aux orchestrates glial autophagy via Atg9 phosphorylation in Parkinson's disease

2021 ◽  
Author(s):  
Shiping Zhang ◽  
Linfang Wang ◽  
Shuanglong Yi ◽  
Shuhua Li ◽  
Honglei Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Risk Factor ◽  
Broad Spectrum ◽  
Critical Component ◽  
Present Evidence ◽  
Tissue Specific ◽  
Pathological Conditions ◽  
Specific Manner ◽  
Cyclin G

Glia serve as double-edged swords to modulate neuropathology in Parkinson's disease (PD), but how they react opposingly to be beneficial or detrimental under pathological conditions, like promote or eliminate α-Synuclein inclusions, remain elusive. Here we present evidence that the PD risk factor Cyclin G-associated kinase (GAK)/dAuxilin (Aux) is a new component in glial autophagy. Lack of GAK/Aux promotes autophagic induction, disrupts lysosome acidification, and blocks glial clearance of substrates. Aux regulates Atg9 trafficking to autophagosomes and lysosomes for autophagosome biogenesis and autolysosome maturation, respectively, via Atg9 phosphorylation at newly identified residues T62 and T69. GAK/Aux-mediated glial autophagy is required for α-Syn degradation and contributes to a broad spectrum of parkinsonian symptoms in Drosophila and mice. Our findings indicate that glial autophagy is a critical component in PD progression and identify a new autophagy factor functioning in a tissue-specific manner; targeting glial autophagy is potentially a therapeutic solution for PD.

scholarly journals Rehabilitation Therapy Utilization in Patients with Parkinson’s Disease in Korea

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Han Gil Seo ◽  
Sang Jun Park ◽  
Jiah Seo ◽  
Seong Jun Byun ◽  
Byung-Mo Oh
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Health Insurance ◽  
Clinical Practice ◽  
Patient Characteristics ◽  
National Sample ◽  
Present Evidence ◽  
Rehabilitation Therapy ◽  
Swallowing Therapy ◽  
Over Time

Objective. Although evidence and guidelines recommend appropriate rehabilitation from the beginning of diagnosis in patients with Parkinson’s disease (PD), there is a lack of data addressing the utilization of rehabilitation therapies for these patients in practice. The aim of this study is to investigate the rate of rehabilitation therapy utilization over time in patients with PD using a nationwide cohort in Korea. Methods. Patients were identified using the registration code for PD in the program for rare, intractable disease from the National Health Insurance Service-National Sample Cohort database, which consists of 979,390 Korean residents. Data were divided into four periods: 2004–2006, 2007–2009, 2010–2012, and 2013–2015. We assessed the utilization of rehabilitation therapies and the associated patient characteristics. Results. The numbers of patients with PD were 384 in 2004, 855 in 2007, 1,023 in 2010, and 1,222 in 2013. The numbers of physiatrist visits per person were 0.58, 0.96, 1.97, and 2.91, in the respective periods. Among the patients, 35–40% had claims for physical therapy, 16–19% for occupational therapy, and 4–6% for swallowing therapy. There were no remarkable differences between these rates between the study periods. Sex, age, income, disability, and levodopa-equivalent dose were significantly associated with the utilization of rehabilitation therapy. Conclusion. This study demonstrated that the rate of rehabilitation therapy utilization did not change remarkably in patients with PD from 2004 to 2015 in Korea although the number of physiatrist visits increased dramatically. The present evidence and guidelines may have not been adequately integrated into clinical practice during the period of study. Additional efforts may be warranted to provide adequate rehabilitation therapies in clinical practice for patients with PD.

scholarly journals Impulse Control Disorders in Parkinson's Disease: Epidemiology, Pathogenesis and Therapeutic Strategies

2021 ◽  
Vol 12 ◽  
Author(s):  
Jun-Fang Zhang ◽  
Xi-Xi Wang ◽  
Ya Feng ◽  
Robert Fekete ◽  
Joseph Jankovic ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Broad Spectrum ◽  
Impulse Control ◽  
Compulsive Buying ◽  
Therapeutic Strategies ◽  
Impulse Control Disorders ◽  
Dopaminergic Therapy ◽  
Disease Epidemiology ◽  
Tremendous Impact

Impulse control disorders (ICDs) in Parkinson's disease (PD) are aberrant behavior such as pathological gambling, hypersexuality, binge eating, and compulsive buying, which typically occur as a result of dopaminergic therapy. Numerous studies have focused on the broad spectrum of ICDs-related behaviors and their tremendous impact on patients and their family members. Recent advances have improved our understanding of ICDs. In this review, we discuss the epidemiology, pathogenesis and treatment of ICDs in the setting of PD.

Variation in the miRNA-433 binding site of FGF20 is a risk factor for Parkinson's disease in Iranian population

2015 ◽  
Vol 355 (1-2) ◽  
pp. 72-74 ◽  
Author(s):  
Leyla Haghnejad ◽  
Babak Emamalizadeh ◽  
Javad Jamshidi ◽  
Alireza Zare Bidoki ◽  
Hamid Ghaedi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Risk Factor ◽  
Binding Site ◽  
Iranian Population

Neuronal microtubules and proteins linked to Parkinson’s disease: a relevant interaction?

2019 ◽  
Vol 400 (9) ◽  
pp. 1099-1112 ◽  
Author(s):  
Alessandra M. Calogero ◽  
Samanta Mazzetti ◽  
Gianni Pezzoli ◽  
Graziella Cappelletti
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Intracellular Trafficking ◽  
Gene Mutations ◽  
Neuronal Loss ◽  
Leucine Rich Repeat ◽  
Microtubule Cytoskeleton ◽  
Pathological Conditions ◽  
Toxin Exposure ◽  
Relevant Interaction

AbstractNeuronal microtubules are key determinants of cell morphology, differentiation, migration and polarity, and contribute to intracellular trafficking along axons and dendrites. Microtubules are strictly regulated and alterations in their dynamics can lead to catastrophic effects in the neuron. Indeed, the importance of the microtubule cytoskeleton in many human diseases is emerging. Remarkably, a growing body of evidence indicates that microtubule defects could be linked to Parkinson’s disease pathogenesis. Only a few of the causes of the progressive neuronal loss underlying this disorder have been identified. They include gene mutations and toxin exposure, but the trigger leading to neurodegeneration is still unknown. In this scenario, the evidence showing that mutated proteins in Parkinson’s disease are involved in the regulation of the microtubule cytoskeleton is intriguing. Here, we focus on α-Synuclein, Parkin and Leucine-rich repeat kinase 2 (LRRK2), the three main proteins linked to the familial forms of the disease. The aim is to dissect their interaction with tubulin and microtubules in both physiological and pathological conditions, in which these proteins are overexpressed, mutated or absent. We highlight the relevance of such an interaction and suggest that these proteins could trigger neurodegeneration via defective regulation of the microtubule cytoskeleton.

Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson’s Disease

2009 ◽  
Vol 256 (3) ◽  
pp. 493-498 ◽  
Author(s):  
C. H. Williams-Gray ◽  
A. Goris ◽  
M. Saiki ◽  
T. Foltynie ◽  
D. A. S. Compston ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Risk Factor ◽  
Apolipoprotein E ◽  
Apolipoprotein E Genotype

scholarly journals Genetic Analysis of LRRK2 R1628P in Parkinson’s Disease in Asian Populations

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yuan Zhang ◽  
Qiying Sun ◽  
Minhan Yi ◽  
Xun Zhou ◽  
Jifeng Guo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Risk Factor ◽  
Chinese Population ◽  
Genetic Factors ◽  
Meta Analysis ◽  
Asian Population ◽  
High Quality ◽  
Asian Populations ◽  
Risk Variants

Although the etiology of Parkinson’s disease (PD) remains unclear, there is increasing evidence of genetic factors contributing to the onset of PD. Various mutations and risk variants of the gene LRRK2 have been reported, but the association between LRRK2 R1628P and PD is still inconsistent. Thus, we conducted a meta-analysis to determine the potential relationship between R1628P and PD. Our study sample was an aggregate of 17 publications, which in total consisted of 9,275 PD patients and 8,114 controls. All of these articles are of high quality according to NOS, and there was no obvious reporting bias or heterogeneity. In a general Asian population, the pooled OR of the risk genotype contrasts was 1.83 (95% CI: 1.57, 2.13). When stratified by ethnicity, the pooled ORs were 1.84 (95% CI: 1.56, 2.18) in a Chinese population and 1.79 (95% CI: 1.27, 2.52) in a non-Chinese population. Our study suggests that LRRK2 R1628P appears to be a risk factor for PD in Asian populations, both Chinese and non-Chinese.

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