A LRRK2/dLRRK-mediated lysosomal pathway that contributes to glial cell death and DA neuron survival

doi:10.1111/tra.12866

	A LRRK2/dLRRK-mediated lysosomal pathway that contributes to glial cell death and DA neuron survival
	Wang, Linfang; Wang, Honglei; Yi, Shuanglong; Zhang, Shiping; Ho, Margaret S.
	2022-10
发表期刊	TRAFFIC
ISSN	1398-9219
EISSN	1600-0854
卷号	23 期号:10 页码:506-520
发表状态	已发表
DOI	10.1111/tra.12866
摘要	Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial and sporadic Parkinson's disease. A plethora of evidence has indicated a role for LRRK2 in endolysosomal trafficking in neurons, while LRRK2 function in glia, although highly expressed, remains largely unknown. Here, we present evidence that LRRK2/dLRRK mediates a lysosomal pathway that contributes to glial cell death and the survival of dopaminergic (DA) neurons. LRRK2/dLRRK knockdown in the immortalized microglia or flies results in enlarged and swelling lysosomes fewer in number. These lysosomes are less mobile, wrongly acidified, exhibit defective membrane permeability and reduced activity of the lysosome hydrolase cathepsin B. In addition, LRRK2/dLRRK depletion causes glial apoptosis, DA neurodegeneration, and locomotor deficits in an age-dependent manner. Taken together, these findings demonstrate a functional role of LRRK2/dLRRK in regulating the glial lysosomal pathway; deficits in lysosomal biogenesis and function linking to glial apoptosis potentially underlie the mechanism of DA neurodegeneration, providing insights on LRRK2/dLRRK function in normal and pathological brains.
关键词	glia homeostasis LRRK2 dLRRK lysosome PD
URL	查看原文
收录类别	SCIE ; SCI
语种	英语
资助项目	National Natural Science Foundation of China["31871039","32170962"]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000853123000001
出版者	WILEY
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/243325
专题	生命科学与技术学院_博士生生命科学与技术学院_PI研究组_何淑君组
通讯作者	Ho, Margaret S.
作者单位	ShanghaiTech Univ, Sch Life Sci & Technol, B416 L Bldg,230 Haike Rd, Shanghai 201210, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Wang, Linfang,Wang, Honglei,Yi, Shuanglong,et al. A LRRK2/dLRRK-mediated lysosomal pathway that contributes to glial cell death and DA neuron survival[J]. TRAFFIC,2022,23(10):506-520.
APA	Wang, Linfang,Wang, Honglei,Yi, Shuanglong,Zhang, Shiping,&Ho, Margaret S..(2022).A LRRK2/dLRRK-mediated lysosomal pathway that contributes to glial cell death and DA neuron survival.TRAFFIC,23(10),506-520.
MLA	Wang, Linfang,et al."A LRRK2/dLRRK-mediated lysosomal pathway that contributes to glial cell death and DA neuron survival".TRAFFIC 23.10(2022):506-520.