scholarly journals The Serine Protease PARK13 Degrading Misfolded Parkinson's Disease Proteins And Confers Cellular Protection

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Indranil Basak ◽  
Ketan Patil ◽  
Jan Petter Larsen ◽  
Simon Møller
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Serine Protease ◽  
Cellular Protection

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

2018 ◽  
Vol 2018 ◽  
pp. 1-1
Author(s):  
Stefano Gambardella ◽  
Rosangela Ferese ◽  
Simona Scala ◽  
Stefania Carboni ◽  
Francesca Biagioni ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Serine Protease ◽  
Di George Syndrome

scholarly journals A lipid switch unlocks Parkinson’s disease-associated ATP13A2

2015 ◽  
Vol 112 (29) ◽  
pp. 9040-9045 ◽  
Author(s):  
Tine Holemans ◽  
Danny Mollerup Sørensen ◽  
Sarah van Veen ◽  
Shaun Martin ◽  
Diane Hermans ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Therapeutic Strategy ◽  
Membrane Surface ◽  
Model Systems ◽  
Molecular Function ◽  
Mitochondrial Stress ◽  
Cellular Protection ◽  
Catalytically Active ◽  
P Type

ATP13A2 is a lysosomal P-type transport ATPase that has been implicated in Kufor–Rakeb syndrome and Parkinson’s disease (PD), providing protection against α-synuclein, Mn2+, and Zn2+ toxicity in various model systems. So far, the molecular function and regulation of ATP13A2 remains undetermined. Here, we demonstrate that ATP13A2 contains a unique N-terminal hydrophobic extension that lies on the cytosolic membrane surface of the lysosome, where it interacts with the lysosomal signaling lipids phosphatidic acid (PA) and phosphatidylinositol(3,5)bisphosphate [PI(3,5)P2]. We further demonstrate that ATP13A2 accumulates in an inactive autophosphorylated state and that PA and PI(3,5)P2 stimulate the autophosphorylation of ATP13A2. In a cellular model of PD, only catalytically active ATP13A2 offers cellular protection against rotenone-induced mitochondrial stress, which relies on the availability of PA and PI(3,5)P2. Thus, the N-terminal binding of PA and PI(3,5)P2 emerges as a key to unlock the activity of ATP13A2, which may offer a therapeutic strategy to activate ATP13A2 and thereby reduce α-synuclein toxicity or mitochondrial stress in PD or related disorders.

scholarly journals Familial Parkinson’s Disease-Associated L166P Mutant DJ-1 is Cleaved by Mitochondrial Serine Protease Omi/HtrA2

2017 ◽  
Vol 33 (6) ◽  
pp. 685-694 ◽  
Author(s):  
Kai Fu ◽  
Yanfei Wang ◽  
Dongkai Guo ◽  
Guanghui Wang ◽  
Haigang Ren
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Serine Protease ◽  
Familial Parkinson’S Disease

scholarly journals Localization of a novel type trypsin-like serine protease, neurosin, in brain tissues of Alzheimer's disease and Parkinson's disease

2000 ◽  
Vol 54 (4) ◽  
pp. 419-426 ◽  
Author(s):  
Kenichi Ogawa ◽  
Tatsuo Yamada ◽  
Yasumi Tsujioka ◽  
Junichi Taguchi ◽  
Mitsuo Takahashi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Serine Protease ◽  
Brain Tissues

scholarly journals Genetic Variations and mRNA Expression of NRF2 in Parkinson’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Caroline Ran ◽  
Karin Wirdefeldt ◽  
Lovisa Brodin ◽  
Mehrafarin Ramezani ◽  
Marie Westerlund ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mrna Expression ◽  
Age Of Onset ◽  
Human Lymphocytes ◽  
Disease Onset ◽  
Cellular Protection ◽  
Expression Levels ◽  
Reverse Transcription Pcr ◽  
Delay Disease Onset

Nuclear factor erythroid 2-like 2 (NRF2) encodes a transcription factor regulating mechanisms of cellular protection and is activated by oxidative stress. NRF2 has therefore been hypothesized to confer protection against Parkinson’s disease and so far an NRF2 haplotype has been reported to decrease the risk of developing disease and delay disease onset. Also NRF2 adopts a nuclear localization in Parkinson’s disease, which is indicative of increased NRF2 activity. We have investigated the association between NRF2 and Parkinson’s disease in a Swedish case-control material and whether NRF2 expression levels correlate with NRF2 genetic variants, disease, or disease onset. Using pyrosequencing, we genotyped one intronic and three promoter variants in 504 patients and 509 control subjects from Stockholm. Further, we quantified NRF2 mRNA expression in EBV transfected human lymphocytes from patients and controls using quantitative real-time reverse transcription PCR. We found that one of the promoter variants, rs35652124, was associated with age of disease onset (Χ2 = 14.19, p value = 0.0067). NRF2 mRNA expression levels however did not correlate with the rs35652124 genotype, Parkinson’s disease, or age of onset in our material. More detailed studies on NRF2 are needed in order to elucidate how this gene affects pathophysiology of Parkinson’s disease.

Evaluation of Efferent Auditory System and Hearing Quality in Parkinson's Disease: Is the Difficulty in Speech Understanding in Complex Listening Conditions Related to Neural Degeneration or Aging?

2020 ◽  
pp. 1-9
Author(s):  
Nuriye Yıldırım Gökay ◽  
Bülent Gündüz ◽  
Fatih Söke ◽  
Recep Karamert
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Auditory System ◽  
Otoacoustic Emissions ◽  
Pure Tone ◽  
Pure Tone Audiometry ◽  
Auditory Pathway ◽  
Normal Hearing ◽  
System Function ◽  
Distortion Product

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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