The APP intracellular domain promotes expression to enable feed-forward neurodegenerative mechanisms in Parkinson's disease.

Gain-of-function mutations in the leucine-rich repeat kinase 2 () gene are common in familial forms of Parkinson's disease (PD), which is characterized by progressive neurodegeneration that impairs motor and cognitive function. We previously demonstrated that LRRK2-mediated phosphorylation of β-amyloid precursor protein (APP) triggers the production and nuclear translocation of the APP intracellular domain (AICD). Here, we connected LRRK2 to AICD in a feed-forward cycle that enhanced LRRK2-mediated neurotoxicity.

Aggregation-induced emission (AIE) nanoparticles labeled human embryonic stem cells (hESCs)-derived neurons for transplantation.

Transplantation of differentiated neurons derived from either human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) is an emerging therapeutic strategy for various neurodegenerative diseases. One important aspect of transplantation is the accessibility to track and control the activity of the stem cells-derived neurons post-transplantation. Recently, the characteristics of organic nanoparticles (NPs) with aggregation-induced emission (AIE) have emerged as efficient cell labeling reagents, where positive outcomes were observed in long-term cancer cell tracing in vivo.

Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease.

Mutations in , which encodes leucine-rich repeat kinase 2, are the most common genetic cause of familial and sporadic Parkinson's disease (PD), a degenerative disease of the central nervous system that causes impaired motor function and, in advanced stages, dementia. Dementia is a common symptom of another neurodegenerative disease, Alzheimer's disease, and research suggests that there may be pathophysiological and genetic links between the two diseases. Aggregates of β amyloid [a protein produced through cleavage of amyloid precursor protein (APP)] are seen in both diseases and in PD patients carrying G2019S-mutant LRRK2.