scholarly journals Noradrenergic Mechanisms in Parkinson’s Disease and L-DOPA-Induced Dyskinesia: Hypothesis and Evidences from Behavioural and Biochemical Studies

10.5772/17435 ◽  
2012 ◽  
Author(s):  
Amal Alachkar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Biochemical Studies

scholarly journals PPM1H phosphatase counteracts LRRK2 signaling by selectively dephosphorylating Rab proteins

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Kerryn Berndsen ◽  
Pawel Lis ◽  
Wondwossen M Yeshaw ◽  
Paulina S Wawro ◽  
Raja S Nirujogi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Phosphatase ◽  
Primary Cilia ◽  
A549 Cells ◽  
Rab Proteins ◽  
Rab Gtpases ◽  
Biochemical Studies ◽  
Cilia Formation ◽  
Human A549

Mutations that activate LRRK2 protein kinase cause Parkinson’s disease. LRRK2 phosphorylates a subset of Rab GTPases within their Switch-II motif controlling interaction with effectors. An siRNA screen of all human protein phosphatases revealed that a poorly studied protein phosphatase, PPM1H, counteracts LRRK2 signaling by specifically dephosphorylating Rab proteins. PPM1H knockout increased endogenous Rab phosphorylation and inhibited Rab dephosphorylation in human A549 cells. Overexpression of PPM1H suppressed LRRK2-mediated Rab phosphorylation. PPM1H also efficiently and directly dephosphorylated Rab8A in biochemical studies. A “substrate-trapping” PPM1H mutant (Asp288Ala) binds with high affinity to endogenous, LRRK2-phosphorylated Rab proteins, thereby blocking dephosphorylation seen upon addition of LRRK2 inhibitors. PPM1H is localized to the Golgi and its knockdown suppresses primary cilia formation, similar to pathogenic LRRK2. Thus, PPM1H acts as a key modulator of LRRK2 signaling by controlling dephosphorylation of Rab proteins. PPM1H activity enhancers could offer a new therapeutic approach to prevent or treat Parkinson’s disease.

scholarly journals Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease

2014 ◽  
Vol 8 ◽  
Author(s):  
Félix J. Jiménez-Jiménez ◽  
Hortensia Alonso-Navarro ◽  
Elena García-Martín ◽  
José A. G. Agúndez
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Biochemical Studies

P.1.a.006 LRRK 2-linked Parkinson's disease: genetic and biochemical studies

2011 ◽  
Vol 21 ◽  
pp. S240
Author(s):  
S. Pchelina ◽  
A. Yakimovskii ◽  
T. Usenko ◽  
A. Emelyanov ◽  
A. Drosdova ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Biochemical Studies

scholarly journals PPM1H phosphatase counteracts LRRK2 signaling by selectively dephosphorylating Rab proteins

2019 ◽  
Author(s):  
Kerryn Berndsen ◽  
Pawel Lis ◽  
Wondwossen Yeshaw ◽  
Paulina S. Wawro ◽  
Raja S. Nirujogi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Phosphatase ◽  
Primary Cilia ◽  
Rab Proteins ◽  
Rab Gtpases ◽  
Knock Out ◽  
High Affinity ◽  
Biochemical Studies ◽  
Cilia Formation

AbstractMutations that activate LRRK2 protein kinase cause Parkinson’s disease. LRRK2 phosphorylates a subset of Rab GTPases within their Switch-II motif controlling interaction with effectors. An siRNA screen of all protein phosphatases revealed that a poorly studied protein phosphatase, PPM1H, counteracts LRRK2 signaling by specifically dephosphorylating Rab proteins. PPM1H knock out increased endogenous Rab phosphorylation and inhibited Rab dephosphorylation. Overexpression of PPM1H suppressed LRRK2-mediated Rab phosphorylation. PPM1H also efficiently and directly dephosphorylated Rab8A in biochemical studies. A “substrate-trapping” PPM1H mutant (Asp288Ala) binds with high affinity to endogenous, LRRK2-phosphorylated Rab proteins, thereby blocking dephosphorylation seen upon addition of LRRK2 inhibitors. PPM1H is localized to the Golgi and its knockdown suppresses primary cilia formation, similar to pathogenic LRRK2. Thus, PPM1H acts as a key modulator of LRRK2 signaling by controlling dephosphorylation of Rab proteins. PPM1H activity enhancers could offer a new therapeutic approach to prevent or treat Parkinson’s disease.

Effect of L-DOPA in a rat model of Parkinson’s disease induced by the selective proteasome inhibitor lactacystin: behavioral and biochemical studies

2012 ◽  
Vol 64 (2) ◽  
pp. 466-467
Author(s):  
Konieczny Jolanta ◽  
Lenda Tomasz ◽  
Czarnecka Anna ◽  
Antkiewicz-Michaluk Lucyna ◽  
Zapała Małgorzata ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Proteasome Inhibitor ◽  
Biochemical Studies
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