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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 | Inhibition of MAP kinase blocks the diffenertiation of Pc-12 cells induced by nerve growth factor显示文摘 | Pang LO Sawada T Decker SJ | 1995 | Joural of Biol Chem1995，270，13： | 1 |
| 3 | Etiological factors of nasopharyngeal carcinoma显示文摘 | Sai Wah Tsao Yim Ling Yip Chi Man Tsang Pei Shin Pang Victoria Ming Yi Lau Guitao Zhang Kwok Wai Lo | 2014 | Oral Oncology2014，，： | 1 |
| 4 | Presence of donor-specific DNA in plasma of kidney and liver-transplant recipients显示文摘 | Lo Y M D Tein M S Pang C C | 1998 | Lancet1998，351，9112： | 1 |
| 5 | Characterization of M-plane GaN film grown on β-LiGaO2 (100) by plasma-assisted molecular beam epitaxy 显示文摘 | SHIH C H LO I PANG W Y | 2011 | Thin Solid Films2011，519，11： | 1 |
| 6 | An empirical study on the correlation between knowledge management ca- pability and competitiveness in Taiwan s industries 显示文摘 | LIU PANG - LO CHEN WEN - CHIN TSAI CHIH - HUNG | 2004 | Technova- tion2004，24，12： | 1 |
| 7 | An Empirical Study on the Correlation Between the Knowledge Management Method and new Product Development Strategy on Product Performance in Taiwan' s Industries 显示文摘 | Pang - Lo Liu Wen- Chin Chen Chih - Hung Tsai | 2005 | Teehnovation2005，，25： | 1 |
| 8 | Presence of donor specific DNA in plasma of kidney and liver transplant recipients 显示文摘 | Lo YMD Tein MSC Pang CCP | 1998 | Lancet1998，351，： | 1 |
| 9 | An empirical study on the correlation between the knowl- edge management method and new product development strategy on product performance in Taiwan' s industries 显示文摘 | Pang - Lo Liu Wen - Chin Chen Chih - Hung Tsai | 2005 | Technovation2005，25，6： | 1 |
| 10 | Dietary behavior and knowledge of dental erosion among Chinese adults显示文摘 | Chu CH Pang KK Lo EC | 2010 | BMC Oral Health2010，10，： | 1 |
| 11 | The biology of EBV infection in human epithelial cells显示文摘 | Sai Wah Tsao Chi Man Tsang Pei Shin Pang Guitao Zhang Honglin Chen Kwok Wai Lo | 2012 | Seminars in Cancer Biology2012，，： | 1 |
| 12 | Presence d donor-specific DNA in plasma of kidney and fiver-transplant recipients 显示文摘 | LO Y M TEIN M S PANG C C | 1998 | Lancet1998，351，9112： | 1 |
| 13 | An em- pirical study on the correlation between the knowledge management method and new product development strat- egy on product performance in Taiwan's industries 显示文摘 | Pang Lo Liu Wen Chin Chen Chih Hung Tsai | 2005 | Technovation2005，25，6： | 1 |
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