| mutant LRRK2 causes neuronal degeneration in both SH-SY5Y cells and primary neurons | |
neurons expressing disease-associated mutant forms of LRRK2 display reduced neurite process length and complexity, tau-positive inclusions with lysosomal features, and ultimately apoptotic cell death |
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neurons deficient in LRRK2 harbor extended neuritic processes with increased branching |
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transgenic Drosophila expressing LRRK2-G2019S mutation display retinal degeneration, selective loss of dopaminergic neurons, locomotor dysfunction, more severe parkinsonism and early mortality |
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LRRK2 transgenic mouse model display an age-dependent and levodopa-responsive slowness of movement associated with diminished dopamine release and axonal pathology of nigrostriatal dopaminergic projection ( |
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transgenic mice that although overexpression of LRRK2 alone did not cause neurodegeneration, the presence of excess LRRK2 greatly accelerated the progression of neuropathological abnormalities developed in PD-related A53T alpha-synuclein transgenic mice ( |
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transgenic mouse strains overexpressing LRRK2 wild-type have elevated striatal dopamine (DA) release with unaltered DA uptake or tissue content, are hyperactive and show enhanced performance in motor function tests ( |
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transgenic mouse strains overexpressing LRRK2 mutant G2019S display an age-dependent decrease in striatal dopamin content, as well as decreased striatal dopamin release and uptake ( |
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dopaminergic system of LRRK2(-/-) mice appears normal, and numbers of dopaminergic neurons and levels of striatal dopamine are unchanged but LRRK2(-/-) kidneys develop striking accumulation and aggregation of alpha-synuclein and ubiquitinated proteins at 20 months of age. loss of LRRK2 dramatically increases apoptotic cell death, inflammatory responses, and oxidative damage ( |
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abnormal dopamine neurotransmission in both hWT and G2019S transgenic LRRK2 mice evidenced by a decrease in extra-cellular dopamine levels ( |
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Mice completely lacking the LRRK2 protein (KO) showed an early-onset marked increase in number and size of secondary lysosomes in kidney proximal tubule cells and lamellar bodies in lung type II cells |
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Mice expressing a LRRK2 kinase-dead mutant (KD) from the endogenous locus displayed similar early-onset pathophysiological changes in kidney but not lung and had had dramatically reduced full-length LRRK2 protein levels in the kidney |
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Knock-in (KI) mice expressing the G2019S PD-associated mutation that increases LRRK2 kinase activity showed none of the LRRK2 protein level and histopathological changes observed in KD and KO mice |