Genetic Predisposition to Parkinson’s Disease and Cancer

2014 ◽  
Vol 14 (3) ◽  
pp. 310-321 ◽  
Author(s):  
Zhiming Li ◽  
Qing Lin ◽  
Qilin Ma ◽  
Congxia Lu ◽  
Chi-Meng Tzeng
Brain ◽  
2020 ◽  
Vol 143 (3) ◽  
pp. 920-931 ◽  
Author(s):  
Samanta Mazzetti ◽  
Milo J Basellini ◽  
Valentina Ferri ◽  
Erica Cassani ◽  
Emanuele Cereda ◽  
...  

Abstract A variety of cellular processes, including vesicle clustering in the presynaptic compartment, are impaired in Parkinson’s disease and have been closely associated with α-synuclein oligomerization. Emerging evidence proves the existence of α-synuclein-related pathology in the peripheral nervous system, even though the presence of α-synuclein oligomers in situ in living patients remains poorly investigated. In this case-control study, we show previously undetected α-synuclein oligomers within synaptic terminals of autonomic fibres in skin biopsies by means of the proximity ligation assay and propose a procedure for their quantification (proximity ligation assay score). Our study revealed a significant increase in α-synuclein oligomers in consecutive patients with Parkinson’s disease compared to consecutive healthy controls (P < 0.001). Proximity ligation assay score (threshold value > 96 using receiver operating characteristic) was found to have good sensitivity, specificity and positive predictive value (82%, 86% and 89%, respectively). Furthermore, to disclose the role of putative genetic predisposition in Parkinson’s disease aetiology, we evaluated the differential accumulation of oligomers in a unique cohort of 19 monozygotic twins discordant for Parkinson’s disease. The significant difference between patients and healthy subjects was confirmed in twins. Intriguingly, although no difference in median values was detected between consecutive healthy controls and healthy twins, the prevalence of healthy subjects positive for proximity ligation assay score was significantly greater in twins than in the consecutive cohort (47% versus 14%, P = 0.019). This suggests that genetic predisposition is important, but not sufficient, in the aetiology of the disease and strengthens the contribution of environmental factors. In conclusion, our data provide evidence that α-synuclein oligomers accumulate within synaptic terminals of autonomic fibres of the skin in Parkinson’s disease for the first time. This finding endorses the hypothesis that α-synuclein oligomers could be used as a reliable diagnostic biomarker for Parkinson’s disease. It also offers novel insights into the physiological and pathological roles of α-synuclein in the peripheral nervous system.


2021 ◽  
Vol 6 (3) ◽  
pp. 78-84
Author(s):  
D. S. Yaroshenko ◽  

The review article presents data on the history of research of extrapyramidal system dysfunctions, modern ideas about the etiology and diagnosis of Parkinson's disease, as the most common disease of the group of extrapyramidal disorders. Currently, no concept of effective therapy for patients with extrapyramidal system dysfunction has been developed, but it has been proven that the probability of developing the disease largely depends on the genetic predisposition and the level of environmental pollution. In the early stages, the disease is slow and asymptomatic, but gradually more than half of patients with Parkinson's disease die, and others need outside care. According to experts, in the near future, Parkinson's disease will become a problem for a significant part of people, because today it affects more and more people of working age. Under such conditions, reliable and early diagnosis of the disease is of great importance, which guarantees timely and most effective treatment. Modern therapies fail to stop the progressive death of the dopaminergic neurons of the substantia nigra, but traditional treatment can achieve symptomatic relief. Currently, it is known that the probability of developing Parkinson's disease depends on the genetic predisposition and the level of man-made environmental stress. The researchers consider that the pathological development of Parkinson's disease in the brain begins in the lower structures of the brain stem with the involvement of the caudal-Rostral nuclei, as well as the involvement of the cortico-basal ganglia-cerebellar pathways. The pathological process affects the ascending pathways and gradually passes to the midbrain, directly to the black substance, spreads from there and weakens the mesocortex and neocortex. Injuries in the brain stem lead to disorganization of the cortico-basal ganglia and cerebellar pathways, followed by the formation of alternative pathways to compensate for the initial disorders in the early stages of the disease. In addition, in Parkinson's disease, intracellular Lewy bodies and neurites formed by the protein alpha-synuclein are created, which are found in the autopsy material of most patients. Poor results of diagnostic evaluation and treatment of Parkinson's disease are usually associated with a lack of understanding of the pathogenesis of Parkinson's disease. The study of the biological basis and pathogenesis of Parkinson's disease is an important task of a whole complex of scientific studies of extrapyramidal system dysfunction. Conclusion. The article discusses the creation of toxic models of Parkinson's disease in vivo and in vitro, which help to recreate the pathogenesis of the disease for early diagnosis and the development of new ways to treat neurodegenerative diseases. In toxic models of Parkinsonism, not only deficits of motor functions such as bradykinesia, tremor, and posture disorders are actively studied, but also non-motor symptoms such as sleep disorders, neuropsychiatric and cognitive abnormalities


2009 ◽  
Vol 22 (6) ◽  
pp. 851-853 ◽  
Author(s):  
Julie Charles ◽  
Isabelle Templier ◽  
Dominique Leroux ◽  
Dimitri Salameire ◽  
Caroline Robert ◽  
...  

1998 ◽  
Vol 76 ◽  
pp. 19
Author(s):  
Y. Mizuno ◽  
S. Matsubayashi ◽  
N. Hattori ◽  
T. Kobayashi ◽  
A. Yoritaka ◽  
...  

2021 ◽  
Author(s):  
Peng Li ◽  
Zuqiang Fu ◽  
Lei Yan ◽  
Ming-yang Du ◽  
Wei-guoLiu

Abstract Background The aetiology of Parkinson's disease (PD) is indistinct, but previous studies of different ethnicities have shown that genetic variations in synuclein alpha (SNCA) have an essential character in the risk of PD. The relation between SNCA intronic single nucleotide polymorphisms (SNPs) and the risk of PD is unclear. Based on the general population and five ethnic groups, this article managed a meta-analysis about the connection of SNCA intronic SNPs with the PD genetic predisposition. Methods This study was implemented according to the 24-step guideline, with strict criteria. The analysis was performed using Stata 16.0 software. Five genetic models were used to analyze the strength of the association, which was quantified by OR value and 95% CI. Results We included 15433 cases and 34143 controls from 31 articles. 6 SNPs in the intron region were screened, and 5 SNPs were statistically significant. Three variants augmented the PD susceptibility (rs2736990, rs3822086, and rs3857059), and two SNPs decreased the risk (rs356186 and rs7684318). Subgroup analysis showed that rs2736990 and rs3822086 carriers added the PD genetic predisposition in the East Asian group. European and Latin group carrying rs3857059 and rs2736990 is the high-risk populations of PD. Conclusions This study finally found 5 SNCA intronic SNPs related to the risk of PD. And racial factors should not be ignored.


Author(s):  
Nuriye Yıldırım Gökay ◽  
Bülent Gündüz ◽  
Fatih Söke ◽  
Recep Karamert

Purpose The effects of neurological diseases on the auditory system have been a notable issue for investigators because the auditory pathway is closely associated with neural systems. The purposes of this study are to evaluate the efferent auditory system function and hearing quality in Parkinson's disease (PD) and to compare the findings with age-matched individuals without PD to present a perspective on aging. Method The study included 35 individuals with PD (mean age of 48.50 ± 8.00 years) and 35 normal-hearing peers (mean age of 49 ± 10 years). The following tests were administered for all participants: the first section of the Speech, Spatial and Qualities of Hearing Scale; pure-tone audiometry, speech audiometry, tympanometry, and acoustic reflexes; and distortion product otoacoustic emissions (DPOAEs) and contralateral suppression of DPOAEs. SPSS Version 25 was used for statistical analyses, and values of p < .05 were considered statistically significant. Results There were no statistically significant differences in the pure-tone audiometry thresholds and DPOAE responses between the individuals with PD and their normal-hearing peers ( p = .732). However, statistically significant differences were found between the groups in suppression levels of DPOAEs and hearing quality ( p < .05). In addition, a statistically significant and positive correlation was found between the amount of suppression at some frequencies and the Speech, Spatial and Qualities of Hearing Scale scores. Conclusions This study indicates that medial olivocochlear efferent system function and the hearing quality of individuals with PD were affected adversely due to the results of PD pathophysiology on the hearing system. For optimal intervention and follow-up, tasks related to hearing quality in daily life can also be added to therapies for PD.


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