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• W3033972556 abstract "Mutations in the gene encoding for leucine-rich repeat kinase 2 (LRRK2) are associated with both familial and sporadic Parkinson´s disease (PD). LRRK2 encodes a large protein comprised of a GTPase and a kinase domain. All pathogenic variants converge on enhancing LRRK2 kinase substrate phosphorylation, and distinct LRRK2 kinase inhibitors are currently in various stages of clinical trials. Although the precise pathophysiological functions of LRRK2 remain largely unknown, PD-associated mutants have been shown to alter various intracellular vesicular trafficking pathways, especially those related to endolysosomal protein degradation events. In addition, biochemical studies have identified a subset of Rab proteins, small GTPases required for all vesicular trafficking steps, as substrate proteins for the LRRK2 kinase activity in vitro and in vivo. Therefore, it is crucial to evaluate the impact of such phosphorylation on neurodegenerative mechanisms underlying LRRK2-related PD, especially with respect to deregulated Rab-mediated endolysosomal membrane trafficking and protein degradation events. Surprisingly, a significant proportion of PD patients due to LRRK2 mutations display neuronal cell loss in the substantia nigra pars compacta in the absence of any apparent α-synuclein-containing Lewy body neuropathology. These findings suggest that endolysosomal alterations mediated by pathogenic LRRK2 per se are not sufficient to cause α-synuclein aggregation. Here, we will review current knowledge about the link between pathogenic LRRK2, Rab protein phosphorylation and endolysosomal trafficking alterations, and we will propose a testable working model whereby LRRK2-related PD may present with variable LB pathology." @default.
• W3033972556 created "2020-06-12" @default.
• W3033972556 creator A5019950626 @default.
• W3033972556 creator A5022990900 @default.
• W3033972556 creator A5037464931 @default.
• W3033972556 creator A5048609114 @default.
• W3033972556 creator A5063147284 @default.
• W3033972556 date "2020-06-04" @default.
• W3033972556 modified "2023-10-16" @default.
• W3033972556 title "LRRK2-Related Parkinson’s Disease Due to Altered Endolysosomal Biology With Variable Lewy Body Pathology: A Hypothesis" @default.
• W3033972556 cites W126348829 @default.
• W3033972556 cites W1518101797 @default.
• W3033972556 cites W1523693806 @default.
• W3033972556 cites W1525474861 @default.
• W3033972556 cites W1547904215 @default.
• W3033972556 cites W1964623101 @default.
• W3033972556 cites W1964976537 @default.
• W3033972556 cites W1969182787 @default.
• W3033972556 cites W1970848642 @default.
• W3033972556 cites W1972097907 @default.
• W3033972556 cites W1973577506 @default.
• W3033972556 cites W1974485263 @default.
• W3033972556 cites W1975229711 @default.
• W3033972556 cites W1975932268 @default.
• W3033972556 cites W1977576077 @default.
• W3033972556 cites W1982330140 @default.
• W3033972556 cites W1983315832 @default.
• W3033972556 cites W1987572257 @default.
• W3033972556 cites W1987899420 @default.
• W3033972556 cites W1989732798 @default.
• W3033972556 cites W1990473626 @default.
• W3033972556 cites W1990478641 @default.
• W3033972556 cites W1992365739 @default.
• W3033972556 cites W1992632425 @default.
• W3033972556 cites W1997163042 @default.
• W3033972556 cites W1999232604 @default.
• W3033972556 cites W2000915110 @default.
• W3033972556 cites W2002599143 @default.
• W3033972556 cites W2005331929 @default.
• W3033972556 cites W2006220351 @default.
• W3033972556 cites W2006875797 @default.
• W3033972556 cites W2006935818 @default.
• W3033972556 cites W2009128541 @default.
• W3033972556 cites W2009556855 @default.
• W3033972556 cites W2010095758 @default.
• W3033972556 cites W2013542960 @default.
• W3033972556 cites W2015589839 @default.
• W3033972556 cites W2017779665 @default.
• W3033972556 cites W2020831499 @default.
• W3033972556 cites W2021097923 @default.
• W3033972556 cites W2021820467 @default.
• W3033972556 cites W2026175550 @default.
• W3033972556 cites W2026253363 @default.
• W3033972556 cites W2026969412 @default.
• W3033972556 cites W2029028848 @default.
• W3033972556 cites W2030725090 @default.
• W3033972556 cites W2036386995 @default.
• W3033972556 cites W2039007685 @default.
• W3033972556 cites W2044407202 @default.
• W3033972556 cites W2044430292 @default.
• W3033972556 cites W2049613365 @default.
• W3033972556 cites W2050647292 @default.
• W3033972556 cites W2052047416 @default.
• W3033972556 cites W2054735667 @default.
• W3033972556 cites W2061995199 @default.
• W3033972556 cites W2063204935 @default.
• W3033972556 cites W2064142522 @default.
• W3033972556 cites W2067064831 @default.
• W3033972556 cites W2067469475 @default.
• W3033972556 cites W2068288454 @default.
• W3033972556 cites W2068495410 @default.
• W3033972556 cites W2070101581 @default.
• W3033972556 cites W2071691594 @default.
• W3033972556 cites W2072216745 @default.
• W3033972556 cites W2072466401 @default.
• W3033972556 cites W2073351779 @default.
• W3033972556 cites W2073449985 @default.
• W3033972556 cites W2073521360 @default.
• W3033972556 cites W2077091529 @default.
• W3033972556 cites W2086698861 @default.
• W3033972556 cites W2087360216 @default.
• W3033972556 cites W2088198588 @default.
• W3033972556 cites W2091821324 @default.
• W3033972556 cites W2095455369 @default.
• W3033972556 cites W2096864428 @default.
• W3033972556 cites W2096905204 @default.
• W3033972556 cites W2099677820 @default.
• W3033972556 cites W2100789202 @default.
• W3033972556 cites W2100867992 @default.
• W3033972556 cites W2100894616 @default.
• W3033972556 cites W2102400397 @default.
• W3033972556 cites W2103000918 @default.
• W3033972556 cites W2103306563 @default.
• W3033972556 cites W2106006107 @default.
• W3033972556 cites W2108175824 @default.
• W3033972556 cites W2108865709 @default.
• W3033972556 cites W2112899867 @default.
• W3033972556 cites W2112905571 @default.
• W3033972556 cites W2115337444 @default.
• W3033972556 cites W2117626437 @default.

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