The LRRK2 gene encodes a protein with an armadillo repeats (ARM) region, an ankyrin repeat (ANK) region, a leucine-rich repeat (LRR) domain, a kinase domain, a RAS domain, a GTPase domain, and a WD40 domain. The protein is present largely in the cytoplasm but also associates with the mitochondrial outer membrane. LRRK2 interacts with the C-terminal R2 RING finger domain of parkin, and parkin interacted with the COR domain of LRRK2. Expression of mutant LRRK2 induced apoptotic cell death in neuroblastoma cells and in mouse cortical neurons. Expression of LRRK2 mutants implicated in autosomal dominant Parkinson's disease causes shortening and simplification of the dendritic tree in vivo and in cultured neurons. This is mediated in part by alterations in macroautophagy, and can be prevented by protein kinase A regulation of the autophagy protein LC3. The G2019S and R1441C mutations elicit post-synaptic calcium imbalance, leading to excess mitochondrial clearance from dendrites by mitophagy. LRRK2 is also a substrate for chaperone-mediated autophagy.
背景文献
1. Usmani A et al. The Cell Biology of LRRK2 in Parkinson\'s Disease. Mol Cell Biol. 2021 Apr
2. Rocha EM et al. LRRK2 and idiopathic Parkinson\'s disease. Trends Neurosci. 2022 Mar
Antigen retrieval: Recommend. The section was pre-treated using heat mediated antigen retrieval with sodium citrate buffer (pH 6.0) for about 2 minutes in microwave oven.
Application: IHC-Fr
Species: Rat
Site: brain
Sample: Frozen section
Antibody concentration: 1/500
Antigen retrieval: Recommend. The section was pre-treated using heat mediated antigen retrieval with sodium citrate buffer (pH 6.0) for about 2 minutes in microwave oven.
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