scholarly journals Frequency of the LRRK2 G2019S mutation in late-onset sporadic patients with Parkinson’s disease

2014 ◽  
Vol 72 (5) ◽  
pp. 356-359 ◽  
Author(s):  
Hsin Fen Chien ◽  
Tamires Rocha Figueiredo ◽  
Marianna Almeida Hollaender ◽  
Fabiano Tofoli ◽  
Leonel Takao Takada ◽  
...  

Mutations in the LRRK2 gene, predominantly G2019S, have been reported in individuals with autosomal dominant inheritance and sporadic Parkinson’s disease (PD). The G2019S mutation has an age-dependent penetrance and evidence shows common ancestry. The clinical manifestations are indistinguishable from idiopathic PD. Its prevalence varies according to the population studied ranging from less than 0.1% in Asians to 41% in North African Arabs. This study aimed to identify G2019S mutation in Brazilian idiopathic PD patients.Method:We sampled 100 PD patients and 100 age- and gender-matched controls. Genetical analysis was accomplished by polymerase chain reaction (PCR).Results:No G2019S mutations were found in both patients with sporadic PD and controls.Conclusions:Our results may be explained by the relatively small sample size.

2019 ◽  
Vol 20 (22) ◽  
pp. 5649 ◽  
Author(s):  
Suh Yee Goh ◽  
Yin Xia Chao ◽  
Shaikali Thameem Dheen ◽  
Eng-King Tan ◽  
Samuel Sam-Wah Tay

Parkinson’s disease (PD) is a disabling neurodegenerative disease that manifests with resting tremor, bradykinesia, rigidity and postural instability. Since the discovery of microRNAs (miRNAs) in 1993, miRNAs have been shown to be important biological molecules involved in diverse processes to maintain normal cellular functions. Over the past decade, many studies have reported dysregulation of miRNA expressions in PD. Here, we identified 15 miRNAs from 34 reported screening studies that demonstrated dysregulation in the brain and/or neuronal models, cerebrospinal fluid (CSF) and blood. Specific miRNAs-of-interest that have been implicated in PD pathogenesis include miR-30, miR-29, let-7, miR-485 and miR-26. However, there are several challenges and limitations in drawing definitive conclusions due to the small sample size in clinical studies, varied laboratory techniques and methodologies and their incomplete penetrance of the blood–brain barrier. Developing an optimal delivery system and unravelling druggable targets of miRNAs in both experimental and human models and clinical validation of the results may pave way for novel therapeutics in PD.


2009 ◽  
Vol 15 (3) ◽  
pp. 242-244 ◽  
Author(s):  
Anna De Rosa ◽  
Chiara Criscuolo ◽  
Pietro Mancini ◽  
Marina De Martino ◽  
Ilaria Anna Giordano ◽  
...  

2009 ◽  
Vol 15 (3) ◽  
pp. 175-180 ◽  
Author(s):  
Biswanath Patra ◽  
Azemat J. Parsian ◽  
Brad A. Racette ◽  
Jing Hua Zhao ◽  
Joel S. Perlmutter ◽  
...  

Author(s):  
Dominic Nadeau ◽  
Isabelle Giroux ◽  
Martine Simard ◽  
Christian Jacques ◽  
Nicolas Dupré

The development of pathological gambling (PG) among people with Parkinson’s disease (PD) is increasingly reported. The intake of dopamine agonists is most often associated with the emergence of this addiction. Although it is known that gambling habits contribute to the onset of gambling problems in the general population, these habits have not yet been studied in individuals with PD. Thus, this study aimed to explore gambling habits in people with PD. Twenty-five individuals with PD and 8 caregivers participated. Thirteen gamblers took part in a semi-structured interview regarding their gambling habits and the presence of a gambling problem and other impulse-control disorders. The results show that gamblers mainly play lotteries and slot machines. Most gamble for pleasure, but some reported wanting to win money to finance a cure for their PD. None of the gamblers involved a caregiver in their gambling activities and no gambler currently presented a gambling problem. However, 2 at-risk gamblers reported having developed a gambling problem in the past. This study sheds light on factors that may contribute to the development of PG among patients with PD, namely, the emergence of new reasons for gambling after a PD diagnosis, erroneous beliefs about gambling, and discretion about gambling habits. Prevention strategies are discussed in view of these results. However, given the small sample size, further studies examining the gambling habits of people with PD are required.RésuméDe plus en plus, on observe le développement du jeu pathologique (JP) chez les personnes atteintes de la maladie de Parkinson (MP). La prise d’agonistes de la dopamine est le plus souvent associée à l’émergence de cette dépendance. Bien qu’il soit connu que les habitudes de jeu contribuent à l’apparition de problèmes de jeu dans la population en général, ces habitudes n’ont pas encore été étudiées chez les personnes atteintes de la maladie de Parkinson (MP). Dans cette optique, cette étude explore les habitudes de jeu chez les personnes atteintes de la MP. Vingt-cinq personnes atteintes de la maladie de Parkinson et huit soignants y ont participé. Treize joueurs ont participé à une entrevue semi-structurée concernant leurs habitudes de jeu et la présence d’un problème de jeu et d’autres troubles liés au contrôle des impulsions. Les résultats montrent que les joueurs jouent principalement aux loteries et aux machines à sous. La plupart jouent par plaisir, mais certains ont déclaré vouloir gagner de l’argent pour financer une thérapie contre la maladie. Aucun des joueurs n’avait avec lui un fournisseur de soins dans ses activités de jeu et aucun joueur ne présentait actuellement de problème de jeu. Cependant, deux joueurs à risque ont déclaré en avoir développé un par le passé. Cette étude met en lumière les facteurs qui peuvent contribuer au développement du jeu pathologique chez les personnes atteintes de Parkinson, à savoir l’émergence de nouvelles raisons pour le jeu après un diagnostic de MP, les croyances erronées sur le jeu et la discrétion sur les habitudes de jeu. Compte tenu de ces résultats, des stratégies de prévention sont analysées. Cependant, étant donné la petite taille de l’échantillon, d’autres études examinant les habitudes de jeu des personnes atteintes de cette maladie sont nécessaires.


Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 505
Author(s):  
Eun-Mi Hur ◽  
Byoung Dae Lee

Parkinson’s disease (PD) is a heterogeneous neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta and the widespread occurrence of proteinaceous inclusions known as Lewy bodies and Lewy neurites. The etiology of PD is still far from clear, but aging has been considered as the highest risk factor influencing the clinical presentations and the progression of PD. Accumulating evidence suggests that aging and PD induce common changes in multiple cellular functions, including redox imbalance, mitochondria dysfunction, and impaired proteostasis. Age-dependent deteriorations in cellular dysfunction may predispose individuals to PD, and cellular damages caused by genetic and/or environmental risk factors of PD may be exaggerated by aging. Mutations in the LRRK2 gene cause late-onset, autosomal dominant PD and comprise the most common genetic causes of both familial and sporadic PD. LRRK2-linked PD patients show clinical and pathological features indistinguishable from idiopathic PD patients. Here, we review cellular dysfunctions shared by aging and PD-associated LRRK2 mutations and discuss how the interplay between the two might play a role in PD pathologies.


2021 ◽  
Vol 11 (6) ◽  
pp. 768
Author(s):  
Tsai-Wei Liu ◽  
Yih-Ru Wu ◽  
Yi-Chun Chen ◽  
Hon Chung Fung ◽  
Chiung-Mei Chen

Background: Studies have suggested that cytokines are crucial mediators in the pathogenesis of Parkinson’s disease (PD). The multifunctional cytokine interleukin (IL)-6 and its single nucleotide polymorphisms (SNPs) were found to have an impact on the development of PD. However, different studies in associations of IL-6 genetic variants with PD showed inconsistent results and it has never been explored in a Taiwanese population. Both IL-1α and IL-8 contribute to the same inflammation pathway. IL-1α genetic polymorphism has an effect on late-onset PD in Taiwan, whereas the associations of IL-8 genetic variants with PD in Taiwan remain to be investigated. Methods: This study examined the frequencies of polymorphisms within the critical promoter areas of the proinflammatory cytokine genes: IL-6 G-174C (rs1800795) and IL-8 A-251T (rs4073) in Taiwanese PD patients compared with age-and gender-matched healthy subjects. Comparisons were also made in genotype and allele frequencies of IL-6 G-174C (rs1800795) and IL-8 A-251T (rs4073) among different populations in previous studies. Results: In total, 1120 subjects, including 509 PD patients (female/male: 259/250) and 511 control subjects (female/male: 252/259), were recruited. We found no statistically significant differences in IL-6 G-174C (rs1800795) or IL-8 A-251T (rs4073) genotypic and allelic distribution between PD and controls, even after being stratified by age at onset and gender. Conclusions: The results did not demonstrate any association of IL-6 G-174C (rs1800795) or IL-8 A-251T (rs4073) with PD in a Taiwanese population. Despite the negative results, this is the first study in associations of IL-6 G-174C (rs1800795) and IL-8 A-251T (rs4073) with PD in Taiwan. The relevance of genetic variants of IL-6 G-174C (rs1800795) or IL-8 A-251T (rs4073) on PD susceptibility warrants further investigation.


2021 ◽  
Author(s):  
Edinson Lucumi Moreno ◽  
Siham Hachi ◽  
Sarah L Nickels ◽  
Kalid IW Kane ◽  
Masha Moein ◽  
...  

Monogenic Parkinson's Disease can be caused by a mutation in the leucine-rich repeat kinase 2 (LRRK2) gene, causing a late-onset autosomal dominant inherited form of Parkinson's Disease. The function of the LRRK2 gene is incompletely understood, but several in vitro studies have reported that LRRK2-G2019S mutations affect neurite branching, calcium homeostasis and mitochondrial function, but thus far, there have been no reports of effects on electrophysiological activity. We assessed the neuronal activity of induced pluripotent stem cell derived neurons from Parkinson's Disease patients with LRRK2-G2019S mutations and isogenic controls. Neuronal activity of spontaneously firing neuronal populations was recorded with a fluorescent calcium-sensitive dye (Fluo-4) and analysed with a novel image analysis pipeline that combined semi-automated neuronal segmentation and quantification of calcium transient properties. Compared with controls, LRRK2-G2019S mutants have shortened inter-spike intervals and an increased rate of spontaneous calcium transient induction.


2020 ◽  
Vol 35 (7) ◽  
pp. 1249-1253 ◽  
Author(s):  
Nurit Omer ◽  
Nir Giladi ◽  
Tanya Gurevich ◽  
Anat Bar‐Shira ◽  
Mali Gana‐Weisz ◽  
...  

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