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| 1 | LRRK2, GBA and their interaction in the regulation of autophagy: implications on therapeutics in Parkinson’s disease显示文摘Mutations in leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA) represent two most common genetic causes of Parkinson’s disease (PD). Both genes are important in the autophagic-lysosomal pathway (ALP), defects of which are associated with α-synuclein (α-syn) accumulation. LRRK2 regulates macroautophagy via activation of the mitogen activated protein kinase/extracellular signal regulated protein kinase (MAPK/ERK) kinase (MEK) and the calcium-dependent adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathways. Phosphorylation of Rab GTPases by LRRK2 regulates lysosomal homeostasis and endosomal trafficking. Mutant LRRK2 impairs chaperone-mediated autophagy, resulting in α-syn binding and oligomerization on lysosomal membranes. Mutations in GBA reduce glucocerebrosidase (GCase) activity, leading to glucosylceramide accumulation, α-syn aggregation and broad autophagic abnormalities. LRRK2 and GBA influence each other: GCase activity is reduced in LRRK2 mutant cells, and LRRK2 kinase inhibition can alter GCase activity in GBA mutant cells. Clinically, LRRK2 G2019S mutation seems to modify the effects of GBA mutation, resulting in milder symptoms than those resulting from GBA mutation alone. However, dual mutation carriers have an increased risk of PD and earlier age of onset compared with single mutation carriers, suggesting an additive deleterious effect on the initiation of PD pathogenic processes. Crosstalk between LRRK2 and GBA in PD exists, but its exact mechanism is unclear. Drugs that inhibit LRRK2 kinase or activate GCase are showing efficacy in pre-clinical models. Since LRRK2 kinase and GCase activities are also altered in idiopathic PD (iPD), it remains to be seen if these drugs will be useful in disease modification of iPD. | Shirley Yin-Yu Pang Rachel Cheuk Nam Lo Philip Wing-Lok Ho Hui-Fang Liu Eunice Eun Seo Chang Chi-Ting Leung Yasine Malki Zoe Yuen-Kiu Choi Wing Yan Wong Michelle Hiu-Wai Kung David Boyer Ramsden Shu-Leong Ho | 2022 | Translational Neurodegeneration2022，11，1： | 2 |
| 2 | Relationship between alloy composition, microstructure and exfoliation corrosion in Al–Zn–Mg–Cu alloys显示文摘 | T. Marlaud B. Malki C. Henon A. Deschamps B. Baroux | 2011 | Corrosion Science2011，，10： | 2 |
| 3 | New design and stability analysis of fuzzy proportion-derivative control systems显示文摘 | | 1994 | IEEE Trans Fuzzy Syst1994，2，3： | 1 |
| 4 | Relationship between alloy composition,microstructure and exfoliation corrosion in Al-Zn-Mg-Cu alloys显示文摘 | Marlaud T Malki B Henon C | 2011 | Corrosion Science2011，53，10： | 1 |
| 5 | Ther mal Healing of the Sub-surface Damage Layer in Sapphire 显示文摘 | MALKI Pinkas HAIMLOTEM YUVALGOLAN | | Materials Chemistry and Physics0，2010，6： | 1 |
| 6 | The expression of C-FABP and PPARgamma and their prognostic significance in prostate cancer显示文摘 | FOROOTAN F S FOROOTAN S S MALKI M I | 2014 | International Journal of On- tology2014，44，1： | 1 |
| 7 | Deep desulp Hurzation of gasoline and diesel fuels using non-hydrogen consuming techniques显示文摘 | ALI M F MALKI A A ALI B E | 2006 | Fuel2006，85，1011： | 1 |
| 8 | Cannulated screw fixation of fractured capitellum:surgical technique through a limited approach显示文摘 | Malki AA Salloom FM Wong-Chung J | 2000 | Injury2000，31，： | 1 |
| 9 | Inhibitory effect of resveratrol on the proliferation of human and rat hepatic derived cell lines显示文摘 | Delmas D Jannin B Malki M C | 2000 | Oncol Rep2000，7，4： | 1 |
| 10 | The role of dyslipidemia on ocular surface,lacrimal and meibomian gland structure and function显示文摘 | Módulo CM Machado Filho EB Malki LT | 2012 | Curr Eye Res2012，37，4： | 1 |
| 11 | Predictive factors of deep abdominal complications after operation for hydatid cyst of the liver: 15 years of experience with 672 patients显示文摘 | E1 Malki Ho El Meidoubi Y Souadka A | 2008 | J Am Coil Surg2008，206，4： | 1 |
| 12 | Short - term electric power load forecasting using feedforward neural networks显示文摘 | Malki H A Karayiannis N B Balasubramanian M | 2004 | Expert Systems2004，21，3： | 1 |
| 13 | Data Ser- vices with uncertain and correlated semantics 显示文摘 | Malki A Benslimane D Benslimane S M | 2016 | World Wide Web2016，19，1： | 1 |
| 14 | Preferen- tial use of an anode as an electron acceptor by an acidophilic bacterium in the presence of oxygerl显示文摘 | MALKI M DE LACEY A L RODR GUEZ N | 2008 | Applied Microbiology andBiotechnology2008，74，14： | 1 |
| 15 | An alternative pathway of imiquimod-induced psoriasis-like skin inflammation in the absence of interleukin-17 receptor a signaling显示文摘 | EI Malki K Karbach SH Huppert J | 2013 | J Invest Dermatol2013，133，2： | 1 |
| 16 | Power Flow Management of Microgrid Networks using Model Predictive Control 显示文摘 | Hooshmand A Malki H A Mohammadpour J | 2012 | Computers & Mathematics with Applications (S0898-1221)2012，64，5： | 1 |
| 17 | Synthesis and cytotoxic activity of MOM-ether analogs of isosteviol显示文摘 | MALKI A LAHA R BERGMEIER S C | 2014 | Bioorganic & Medicinal Chemistry Letters2014，24，4： | 1 |
| 18 | An algorithm for managing warfarin resistance 显示文摘 | Osinbowale O Malki M A Schade A | 2009 | Cleveland Clin J Med2009，76，12： | 1 |
| 19 | Carbonatite melts and electrical conductivity in the asthenosphere显示文摘 | Gaillard F Malki M Iacono Marziano G | 2008 | Sci ence2008，322，： | 1 |
| 20 | An algorithm for managing warfarin resistance显示文摘 | Osinbowale O A1 Malki M Schade A | 2009 | Cleve Clin J Med2009，76，12： | 1 |
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