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Title[redir]:
Interplay of LRRK2 with chaperone-mediated autophagy - PMC
Description:
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson’s disease (PD). In this work, we demonstrate that LRRK2 can be degraded in lysosomes by chaperone-mediated autophagy (CMA), whereas the most common ...
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Keywords {🔍}
lrrk, cma, fig, lysosomes, cells, lysosomal, doi, binding, lampa, αsyn, proteins, degradation, protein, mutant, membrane, gslrrk, pubmed, google, scholar, supplementary, levels, pmc, control, article, substrates, kinase, presence, activity, free, neurons, effect, neuronal, brain, wtlrrk, autophagy, observed, substrate, incubated, patients, shown, mice, expressing, brains, increase, isolated, uptake, association, hsc, reduced, gapdh,
Topics {✒️}
cma reporter kferq-pa-mcherry133 regulates chaperone-mediated autophagy kferq-pa-mcherry1 fluorescent reporter fluorescent kferq-pa-mcherry1 reporter wild-type alpha-synuclein wild type alpha-synuclein chaperone-mediated autophagy samantha monitor chaperone-mediated autophagy track chaperone-mediated autophagy transferring sds-page gels phosphorylated erk/map kinases gfp-tagged full length chaperone-mediated autophagy markers full-length blots/gels fluorophore-conjugated secondary antibodies23 initial acid-insoluble radioactivity ipsc-derived dopaminergic neurons lysosome-enriched fractions isolated pmc beta search online methods animals 12h light/dark cycle colocalization lamp-2a/ α-syn rab7-dependent lysosomal positioning mutant alpha-synuclein gfp-tagged truncated forms human ips-based models α-syn abnormally accumulates44 distal c-terminal motifs ipsc-derived neuronal cells age-related disorders resulting lamp-2a takes place22 bonferroni post-hoc test substrate-induced lysosomal binding age-matched control individuals wild-type α-syn pd patient-derived cells lamp-2a multimerization leads glyceraldehyde-3-phosphate dehydrogenase sh-sy5y cells untreated higher lysosome-binding affinity pathogenic α-syn mutant chaperone-mediated autophagy exogenously added α-syn plasmids expressing wild-type increased α-syn content mutant α-syn variant early pre-symptomatic states cma substrate-dependent manner differentiated sh-sy5y cells mutant α-syn proteins
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