Results 11 to 20 of about 19,899 (238)

LRRK2 interactions with microtubules are independent of LRRK2-mediated Rab phosphorylation

EMBO Reports
Deregulated microtubules are common defects associated with neurodegenerative diseases. Recent cryo-electron microscopy studies in cell lines overexpressing Parkinson’s disease-associated LRRK2 suggest microtubule surfaces may regulate kinase activity by
Tuyana Malankhanova, Zhiyong Liu, Enquan Xu, Nicole Bryant, Ki Woon Sung, Huizhong Li, Samuel Strader, Andrew B West   +7 more
doaj   +4 more sources

Disrupted TFEB/GDNF-cAMP/ATP Coupling Underlies Astrocytic Dysfunction and Depression in LRRK2 G2019S Parkinson's Mice. [PDF]

Adv Sci (Weinh)
ABSTRACT The LRRK2 G2019S mutation, a Parkinson's disease–linked variant, has been associated with depression‐like phenotypes, but mechanisms remain unclear. We chart age‐dependent behavioral changes and astrocyte reactivity in G2019S mice and define a pathway connecting LRRK2 to TFEB/GDNF signaling, cellular energetics, and inflammation.
Yao L, Hatami M, Koc S, Jiang Q, Skutella T, Zhang Y.   +5 more
europepmc   +2 more sources

The LRRK2 signalling system [PDF]

Cell and Tissue Research, 2018
The LRRK2 gene is a major contributor to genetic risk for Parkinson's disease and understanding the biology of the leucine-rich repeat kinase 2 (LRRK2, the protein product of this gene) is an important goal in Parkinson's research. LRRK2 is a multi-domain, multi-activity enzyme and has been implicated in a wide range of signalling events within the ...
Price, Alice, Manzoni, Claudia, Cookson, Mark R., Lewis, Patrick A.   +3 more
core   +5 more sources

LRRK2 Kinase Activity Is Dependent on LRRK2 GTP Binding Capacity but Independent of LRRK2 GTP Binding

PLoS ONE, 2011
Leucine rich repeat kinase 2 (LRRK2) is a Parkinson's disease (PD) gene that encodes a large multidomain protein including both a GTPase and a kinase domain. GTPases often regulate kinases within signal transduction cascades, where GTPases act as molecular switches cycling between a GTP bound "on" state and a GDP bound "off" state. It has been proposed
Jean-Marc Taymans, Renée Vancraenenbroeck, Petri Ollikainen, Alexandra Beilina, Evy Lobbestael, Marc De Maeyer, Veerle Baekelandt, Mark R Cookson   +7 more
openaire   +5 more sources

LRRK2 expression is enriched in the striosomal compartment of mouse striatum

Neurobiology of Disease, 2012
In spite of a clear genetic link between Parkinson's disease (PD) and mutations in LRRK2, cellular localization and physiological function of LRRK2 remain debated. Here we demonstrate the immunohistochemical localization of LRRK2 in adult mouse and early
Bart de Strooper, Wim Mandemakers, An Snellinx   +2 more
exaly   +3 more sources

Computational analysis of the LRRK2 interactome [PDF]

PeerJ, 2015
LRRK2 was identified in 2004 as the causative protein product of the Parkinson's disease locus designated PARK8. In the decade since then, genetic studies have revealed at least 6 dominant mutations in LRRK2 linked to Parkinson's disease, alongside one associated with cancer.
Manzoni, C, Denny, P, Lovering, RC, Lewis, PA   +3 more
openaire   +6 more sources

Fbxl18 targets LRRK2 for proteasomal degradation and attenuates cell toxicity

Neurobiology of Disease, 2017
Dominantly inherited mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common causes of familial Parkinson's disease (PD) and LRRK2 polymorphisms are associated with increased risk for idiopathic PD.
Matthew Goldberg, Sandeep Kumar Barodia, Xiaodong Ding   +2 more
exaly   +3 more sources

LRRK2 Phosphorylation: Behind the Scenes [PDF]

The Neuroscientist, 2018
Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are known today as the most common genetic cause of Parkinson’s disease (PD). LRRK2 is a large protein that is hypothesized to regulate other proteins as a scaffold in downstream signaling pathways.
De Wit, Tina, Baekelandt, Veerle, Lobbestael, Evy   +2 more
openaire   +3 more sources

Inhibition of LRRK2 or Casein Kinase 1 Results in LRRK2 Protein Destabilization [PDF]

Molecular Neurobiology, 2018
Mutations and variations in the leucine-rich repeat kinase 2 (LRRK2) gene are strongly associated with an increased risk to develop Parkinson's disease (PD). Most pathogenic LRRK2 mutations display increased kinase activity, which is believed to underlie LRRK2-mediated toxicity.
De Wit, Tina, Baekelandt, Veerle, Lobbestael, Evy   +2 more
openaire   +4 more sources

Gene Correction Enhances Dopaminergic Cell Therapy in a Nonhuman Primate Model of Parkinson's Disease. [PDF]

Adv Sci (Weinh)
LRRK2‐mutant induced pluripotent stem cells (iPSCs) were derived from a patient with Parkinson's disease (PD). Using CRISPR/Cas9–mediated gene editing, the pathogenic LRRK2 mutations were precisely corrected, and isogenic dopaminergic neural progenitor cells (DA‐NPCs) were subsequently generated.
Yan Q, Xu C, Gao J, Wang P, Wu Q, Jin Y, Lu B, Li M, Shao M, Li B, Su Z, Zhang Y, Chen J, An H, Huang M, Zhuang X, Shen Y, Wang F, Xu N, Liu Y, Tang L, Zhong X, Zhong M, Chen J, Wang Z, Luo X, Liu S, Liu R, Zhang L, Rao J.   +29 more
europepmc   +2 more sources