scholarly journals Inhibition of FK506 Binding Proteins Reduces  -Synuclein Aggregation and Parkinson's Disease-Like Pathology

2010 ◽  
Vol 30 (7) ◽  
pp. 2454-2463 ◽  
Author(s):  
M. Gerard ◽  
A. Deleersnijder ◽  
V. Daniels ◽  
S. Schreurs ◽  
S. Munck ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Binding Proteins ◽  
Fk506 Binding Proteins

Increased Striatal mRNA and Protein Levels of the Immunophilin FKBP-12 in Experimental Parkinson's Disease and Identification of FKBP-12-Binding Proteins

2007 ◽  
Vol 6 (10) ◽  
pp. 3952-3961 ◽  
Author(s):  
Anna Nilsson ◽  
Karl Sköld ◽  
Benita Sjögren ◽  
Marcus Svensson ◽  
Johan Pierson ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Binding Proteins ◽  
Protein Levels

scholarly journals Parkinson’s disease is associated with altered expression of CaV1 channels and calcium-binding proteins

Brain ◽  
2013 ◽  
Vol 136 (7) ◽  
pp. 2077-2097 ◽  
Author(s):  
Michael J. Hurley ◽  
Bianca Brandon ◽  
Steve M. Gentleman ◽  
David T. Dexter
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Calcium Binding ◽  
Binding Proteins ◽  
Calcium Binding Proteins ◽  
Altered Expression

scholarly journals Switching on Endogenous Metal Binding Proteins in Parkinson’s Disease

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 179 ◽  
Author(s):  
Fleur McLeary ◽  
Alexandre Rcom-H’cheo-Gauthier ◽  
Michael Goulding ◽  
Rowan Radford ◽  
Yuho Okita ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Vitamin D ◽  
Parkinson's Disease ◽  
Metal Binding ◽  
Binding Proteins ◽  
Binding Protein ◽  
Cytoplasmic Inclusions ◽  
Endogenous Expression ◽  
Parkinson’S Diseases ◽  
Neuroprotective Strategy

The formation of cytotoxic intracellular protein aggregates is a pathological signature of multiple neurodegenerative diseases. The principle aggregating protein in Parkinson’s disease (PD) and atypical Parkinson’s diseases is α-synuclein (α-syn), which occurs in neural cytoplasmic inclusions. Several factors have been found to trigger α-syn aggregation, including raised calcium, iron, and copper. Transcriptional inducers have been explored to upregulate expression of endogenous metal-binding proteins as a potential neuroprotective strategy. The vitamin-D analogue, calcipotriol, induced increased expression of the neuronal vitamin D-dependent calcium-binding protein, calbindin-D28k, and this significantly decreased the occurrence of α-syn aggregates in cells with transiently raised intracellular free Ca, thereby increasing viability. More recently, the induction of endogenous expression of the Zn and Cu binding protein, metallothionein, by the glucocorticoid analogue, dexamethasone, gave a specific reduction in Cu-dependent α-syn aggregates. Fe accumulation has long been associated with PD. Intracellularly, Fe is regulated by interactions between the Fe storage protein ferritin and Fe transporters, such as poly(C)-binding protein 1. Analysis of the transcriptional regulation of Fe binding proteins may reveal potential inducers that could modulate Fe homoeostasis in disease. The current review highlights recent studies that suggest that transcriptional inducers may have potential as novel mechanism-based drugs against metal overload in PD.

scholarly journals Regulation of Iron Homeostasis Through Parkin-mediated Lactoferrin Ubiquitylation

2020 ◽  
Author(s):  
Ankur A. Gholkar ◽  
Stefan Schmollinger ◽  
Erick F. Velasquez ◽  
Yu-Chen Lo ◽  
Whitaker Cohn ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ubiquitin Ligase ◽  
Neurodegenerative Disorders ◽  
Iron Homeostasis ◽  
Binding Proteins ◽  
Somatic Mutations ◽  
Iron Binding ◽  
Ubiquitin Ligase Activity ◽  
Iron Binding Proteins

ABSTRACTSomatic mutations that perturb Parkin ubiquitin ligase activity and the misregulation of iron homeostasis have both been linked to Parkinson’s disease. Lactotransferrin is a member of the transferrin iron binding proteins that regulate iron homeostasis and increased levels of Lactotransferrin and its receptor have been observed in neurodegenerative disorders like Parkinson’s disease. Here, we report that Parkin binds to Lactotransferrin and ubiquitylates it to regulate iron homeostasis.

scholarly journals Calmodulin and Its Binding Proteins in Parkinson’s Disease

2021 ◽  
Vol 22 (6) ◽  
pp. 3016
Author(s):  
Anastasiia Bohush ◽  
Wiesława Leśniak ◽  
Serge Weis ◽  
Anna Filipek
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Binding Proteins ◽  
Neurodegenerative Disorder ◽  
Lewy Bodies ◽  
Synaptic Proteins ◽  
Muscle Rigidity ◽  
Cellular Processes ◽  
Intracellular Signals

Parkinson’s disease (PD) is a neurodegenerative disorder that manifests with rest tremor, muscle rigidity and movement disturbances. At the microscopic level it is characterized by formation of specific intraneuronal inclusions, called Lewy bodies (LBs), and by a progressive loss of dopaminergic neurons in the striatum and substantia nigra. All living cells, among them neurons, rely on Ca2+ as a universal carrier of extracellular and intracellular signals that can initiate and control various cellular processes. Disturbances in Ca2+ homeostasis and dysfunction of Ca2+ signaling pathways may have serious consequences on cells and even result in cell death. Dopaminergic neurons are particularly sensitive to any changes in intracellular Ca2+ level. The best known and studied Ca2+ sensor in eukaryotic cells is calmodulin. Calmodulin binds Ca2+ with high affinity and regulates the activity of a plethora of proteins. In the brain, calmodulin and its binding proteins play a crucial role in regulation of the activity of synaptic proteins and in the maintenance of neuronal plasticity. Thus, any changes in activity of these proteins might be linked to the development and progression of neurodegenerative disorders including PD. This review aims to summarize published results regarding the role of calmodulin and its binding proteins in pathology and pathogenesis of PD.

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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