Abstract
Neurodegeneration Parkinson's disease is a progressive neurodegenerative disorder that is commonly associated with activating mutations in the kinase LRRK2. The disease results in dementia owing to loss of dopaminergic neurons. Chen et al. discovered why activating LRRK2 mutations are toxic to neurons. When phosphorylated by mutant LRRK2, a cleavage product of amyloid precursor protein (APP) translocated to the nucleus and was more transcriptionally active, which killed the dopaminergic neurons. These findings connect the pathology of Parkinson's to that of Alzheimer's disease, in which dementia is associated with another APP cleavage product, β-amyloid. Sci. Signal. 10 , eaam6790 (2017).
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