Publications

Latest publication 04/01/2022

Deubiquitinase CYLD acts as a negative regulator of dopamine neuron survival in

Mutations in PINK1 and parkin highlight the mitochondrial axis of ParkinsonÕs disease (PD) pathogenesis. PINK1/parkin regulation of the...

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    [title] => Deubiquitinase CYLD acts as a negative regulator of dopamine neuron survival in 
    [paragraph] => Deubiquitinase CYLD acts as a negative regulator of dopamine neuron survival in Parkinson's disease
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Authors
SK Pirooznia, H Wang, N Panicker et al

 Lab
Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Journal
Science Advances
Abstract
Mutations in PINK1 and parkin highlight the mitochondrial axis of ParkinsonÕs disease (PD) pathogenesis. PINK1/parkin regulation of the transcriptional repressor PARIS bears direct relevance to dopamine neuron survival through augmentation of PGC-1_Ðdependent mitochondrial biogenesis. Notably, knockout of PARIS attenuates dopaminergic neurodegeneration in mouse models, indicating that interventions that prevent dopaminergic accumulation of PARIS could have therapeutic potential in PD. To this end, we have identified the deubiquitinase cylindromatosis (CYLD) to be a regulator of PARIS protein stability and proteasomal degradation via the PINK1/parkin pathway. Knockdown of CYLD in multiple models of PINK1 or parkin inactivation attenuates PARIS accumulation by modulating its ubiquitination levels and relieving its repressive effect on PGC-1_ to promote mitochondrial biogenesis. Together, our studies identify CYLD as a negative regulator of dopamine neuron survival, and inhibition of CYLD may potentially be beneficial in PD by lowering PARIS levels and promoting mitochondrial biogenesis.
BIOSEB Instruments Used
Grip strength test (BIO-GS3)
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An easy way to objectively quantify the muscular strength of mice and rats, and to assess the effect of drugs, toxins, muscular (i.e. myopathy) and neurodegenerative diseases on muscular degeneration. It is widely used in conjunction with the ROTAROD motor coordination test: a normally coordinated rodent will show a decreased latency to fall off the rotating rod if its muscular strength is low. The Grip Strength Test is a must for your research on activity, motor control & coordination, and is particularly well suited for studies on Parkinson's & Huntington's disease.
New features GS4 - 2023: Color display with permanent backlight screen for easier reading, reset by footswitch, Improved battery time, Larger data memory of 500 values, Animal counter, USB port (charging/data transfer)

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