Publications

Dernière publication 01/04/2022

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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Une méthode simple pour quantifier objectivement la force musculaire des rats et souris et l'effet de drogues, toxines, maladies musculaires (ex: myopathie) et neurodégénératives. Cette mesure de force est souvent employée en association avec le test de coordination motrice ROTAROD: un sujet présentant une coordination normale montrera des résultats médiocres en cas de faible force musculaire. Un must pour vos recherches sur l'activité, la coordination et le contrôle musculaire: particulièrement utile pour vos études sur les maladies de Parkinson et Huntington.
Nouveautés GS4 - 2023: Écran couleur rétroéclairé (meilleure lisibilité), pédale de remise à zéro, durée de batterie optimisée, taille de mémoire augmentée à 500 valeurs, compteur d'animaux, port USB (transfert de données/charge)

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