scholarly journals Mitochondrial Serine Protease HTRA2 p.G399S in a Female with Di George Syndrome and Parkinson’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Stefano Gambardella ◽  
Rosangela Ferese ◽  
Simona Scala ◽  
Stefania Carboni ◽  
Francesca Biagioni ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Risk Factor ◽  
Sequencing Analysis ◽  
Pathogenetic Role ◽  
Number Of Patients ◽  
History Of ◽  
Early Onset Parkinson’S Disease ◽  
Di George Syndrome

Deletion at 22q11.2 responsible for Di George syndrome (DGs) is a risk factor for early-onset Parkinson’s disease (EOPD). To date, all patients reported with 22q11.2 deletions and parkinsonian features are negative for a family history of PD, and possible mutations in PD-related genes were not properly evaluated. The goal of this paper was to identify variants in PD genes that could contribute, together with 22q11.2 del, to the onset of parkinsonian features in patients affected by Di George syndrome. To this aim, sequencing analysis of 4800 genes including 17 PD-related genes was performed in a patient affected by DGs and EOPD. The analysis identified mutation p.Gly399Ser in OMI/HTRA2 (PARK13). To date, the mechanism that links DGs with parkinsonian features is poorly understood. The identification of a mutation in a PARK gene suggests that variants in PD-related genes, or in genes still not associated with PD, could contribute, together with deletion at 22q11.2, to the EOPD in patients affected by DGs. Further genetic analyses in a large number of patients are strongly required to understand this mechanism and to establish the pathogenetic role of p.Gly399Ser in OMI/HTRA2.

scholarly journals Comprehensive assessment of PINK1 variants in Parkinson’s disease

2020 ◽  
Author(s):  
Lynne Krohn ◽  
Francis P. Grenn ◽  
Mary B. Makarious ◽  
Jonggeol Jeffrey Kim ◽  
Sara Bandres-Ciga ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Risk Factor ◽  
Autosomal Recessive ◽  
Disease Susceptibility ◽  
Large Datasets ◽  
The Past ◽  
Increased Risk ◽  
Early Onset Parkinson’S Disease

AbstractMultiple genes have been associated with monogenic Parkinson’s disease and Parkinsonism syndromes. Mutations in PINK1 (PARK6) have been shown to result in autosomal recessive early onset Parkinson’s disease. In the past decade, several studies have suggested that carrying a single heterozygous PINK1 mutation is associated with increased risk for Parkinson’s disease. Here we comprehensively assess the role of PINK1 variants in Parkinson’s disease susceptibility using several large datasets totalling 376,558 individuals including: 13,708 Parkinson’s disease cases and 362,850 controls. After combining these data, we did not find evidence to support a role for heterozygous PINK1 mutations as a risk factor for Parkinson’s disease.

scholarly journals The Role of the Dopamine β-hydroxylase Functional Polymorphism in Patients with Early-Onset Parkinson’s Disease in the Turkish Population

2021 ◽  
Vol 27 (1) ◽  
pp. 21-26
Author(s):  
Sevda Erer ◽  
Işıl Ezgi Eryılmaz ◽  
Dilara Kamer Çolak ◽  
Ünal Egeli ◽  
Gülşah Çeçener ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Onset ◽  
Turkish Population ◽  
Functional Polymorphism ◽  
Early Onset Parkinson’S Disease

scholarly journals Early-onset Parkinson's disease and depression

2007 ◽  
Vol 65 (1) ◽  
pp. 5-10 ◽  
Author(s):  
Délcio Bertucci Filho ◽  
Hélio A.G. Teive ◽  
Lineu C. Werneck
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Risk Factor ◽  
Parkinson Disease ◽  
Early Onset ◽  
Clinical Characteristics ◽  
Late Onset ◽  
Mild Depression ◽  
Moderate Depression ◽  
Early Onset Parkinson’S Disease

Patients with Parkinson’s disease (PD) in whom symptoms start before the age of 45 years (EOPD) present different clinical characteristics from those with the late-onset form of the disease. The incidence of depression is believed to be greater in patients with EOPD than with the late-onset form of the disease, although there is no risk factor or marker for depression in patients with PD. We studied 45 patients with EOPD to define the frequency of depression and to identify possible differences between the groups with and without depression. Depression was diagnosed in 16 (35.5%) of the patients, a higher incidence than in the population at large but similar to the figure for late-onset Parkinson disease; 8 (50%) of the patients had mild depression, 4 (25%) moderate depression and 4 (25%) were in remission. There was no relationship between depression and any of the clinical characteristics of the disease, although the EOPD patients with depression presented earlier levodopa-related complications and were more affected on the Hoehn-Yahr, UPDRS and Schwab-England scales.

scholarly journals Reward learning deficits in Parkinson's disease depend on depression

2017 ◽  
Vol 47 (13) ◽  
pp. 2302-2311 ◽  
Author(s):  
M. H. M. Timmer ◽  
G. Sescousse ◽  
M. E. van der Schaaf ◽  
R. A. J. Esselink ◽  
R. Cools
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Reversal Learning ◽  
Learning Deficits ◽  
Medication Withdrawal ◽  
History Of ◽  
Depression History ◽  
Non Motor Symptoms ◽  
History Of Depression

BackgroundDepression is one of the most common and debilitating non-motor symptoms of Parkinson's disease (PD). The neurocognitive mechanisms underlying depression in PD are unclear and treatment is often suboptimal.MethodsWe investigated the role of striatal dopamine in reversal learning from reward and punishment by combining a controlled medication withdrawal procedure with functional magnetic resonance imaging in 22 non-depressed PD patients and 19 PD patients with past or present depression.ResultsPD patients with a depression (history) exhibited impaired reward v. punishment reversal learning as well as reduced reward v. punishment-related BOLD signal in the striatum (putamen) compared with non-depressed PD patients. No effects of dopaminergic medication were observed.ConclusionsThe present findings demonstrate that impairments in reversal learning from reward v. punishment and associated striatal signalling depend on the presence of (a history of) depression in PD.

scholarly journals Reward learning deficits in Parkinson’s disease depend on depression

2016 ◽  
Author(s):  
Monique H.M. Timmer ◽  
Guillaume Sescousse ◽  
Marieke E. van der Schaaf ◽  
Rianne A.J. Esselink ◽  
Roshan Cools
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Reversal Learning ◽  
Learning Deficits ◽  
Medication Withdrawal ◽  
History Of ◽  
Depression History ◽  
Non Motor Symptoms ◽  
History Of Depression

AbstractBackgroundDepression is one of the most common and debilitating non-motor symptoms of Parkinson’s disease (PD). The neurocognitive mechanisms underlying depression in PD are unclear and treatment is often suboptimal.MethodsWe investigated the role of striatal dopamine in reversal learning from reward and punishment by combining a controlled medication withdrawal procedure with functional magnetic resonance imaging (fMRI) in 22 non-depressed PD patients and 19 PD patients with past or present PD-related depression.ResultsPD patients with a PD-related depression (history) exhibited impaired reward versus punishment reversal learning as well as reduced reward versus punishment-related BOLD signal in the striatum (putamen) compared with non-depressed PD patients. No effects of dopaminergic medication were observed.ConclusionsThe present findings demonstrate that impairments in reversal learning from reward versus punishment and associated reward-related striatal signalling depend on the presence of (a history of) depression in PD.

scholarly journals Parkin is recruited selectively to impaired mitochondria and promotes their autophagy

2008 ◽  
Vol 183 (5) ◽  
pp. 795-803 ◽  
Author(s):  
Derek Narendra ◽  
Atsushi Tanaka ◽  
Der-Fen Suen ◽  
Richard J. Youle
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mammalian Cells ◽  
Loss Of Function ◽  
Gene Coding ◽  
Selective Elimination ◽  
Mitochondrial Toxins ◽  
Early Onset Parkinson’S Disease ◽  
Increased Susceptibility

Loss-of-function mutations in Park2, the gene coding for the ubiquitin ligase Parkin, are a significant cause of early onset Parkinson's disease. Although the role of Parkin in neuron maintenance is unknown, recent work has linked Parkin to the regulation of mitochondria. Its loss is associated with swollen mitochondria and muscle degeneration in Drosophila melanogaster, as well as mitochondrial dysfunction and increased susceptibility to mitochondrial toxins in other species. Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. After recruitment, Parkin mediates the engulfment of mitochondria by autophagosomes and the selective elimination of impaired mitochondria. These results show that Parkin promotes autophagy of damaged mitochondria and implicate a failure to eliminate dysfunctional mitochondria in the pathogenesis of Parkinson's disease.

Progressive Dopamine Neuron Loss in Parkinson's Disease: The Multiple Hit Hypothesis

2006 ◽  
Vol 15 (3) ◽  
pp. 239-250 ◽  
Author(s):  
Paul M. Carvey ◽  
Ashok Punati ◽  
Mary B. Newman
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Risk Factor ◽  
Animal Models ◽  
Postnatal Exposure ◽  
New Era ◽  
Progressive Loss ◽  
History Of ◽  
6 Hydroxydopamine ◽  
Multiple Hit

Animal models have been an essential tool for researchers and clinicians in their efforts to study and treat Parkinson's disease (PD). Thus, the various ways 6-hydroxydopamine is employed, the use of MPTP in rodents and nonhuman primates, the prenatal exposure to bacterial endotoxin, the postnatal exposure to environmental toxins such as paraquat and rotenone, the assessment of dopamine (DA) neurons in genetic knockout mouse, and even the behavioral analysis of fruit flies and worms have added significantly to our knowledge base of PD—or have they? Are these animal models manifesting a true model of PD? Have the 7786 published studies (to date) on PD with animal models led to a clearer understanding of its etiology, treatment, or progression? In this review we critically assess this question. We begin with a succinct history of the major contributions, which have led to the current animal models of PD. We then evaluate the primary issue of the progressive loss of DA neurons, which, except for a few studies, has not been addressed in animal models of PD, even though this is the major pathological characteristic of the disease. Lastly, we discuss the possibility that more than one risk factor for PD may be necessary to develop an animal model that shows synergy—the progressive loss of DA neurons. Thus, the multiple hit hypothesis of PD—that is, the effect of more then one risk factor—may be the start of new era in animal models of PD that is one step closer to mimicking the pathology of PD in humans.

Evaluating the Role of SNCA , LRRK2 , and GBA in Chinese Patients With Early‐Onset Parkinson's Disease

2020 ◽  
Vol 35 (11) ◽  
pp. 2046-2055 ◽  
Author(s):  
Yongping Chen ◽  
Xiaojing Gu ◽  
Ruwei Ou ◽  
Lingyu Zhang ◽  
Yanbing Hou ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Onset ◽  
Chinese Patients ◽  
Early Onset Parkinson’S Disease
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