A novel 14-3-3θ phosphomimetic mouse model demonstrates social dominance defects.

14-3-3 proteins, particularly the 14-3-3θ isoform, are neuroprotective in several models of Parkinson's disease (PD). Evidence for increased 14-3-3θ phosphorylation observed in PD and other neurodegenerative diseases points to a possible pathogenic role for 14-3-3θ phosphorylation in neurodegenerative disease. We recently created a novel conditional knock-in mouse to express the 14-3-3θ S232D phosphomimetic mutation.

14-3-3 mitigates alpha-synuclein aggregation and toxicity in the in vivo preformed fibril model.

Alpha-synuclein (αsyn) is the key component of proteinaceous aggregates termed Lewy Bodies that pathologically define a group of disorders known as synucleinopathies, including Parkinson's Disease (PD) and Dementia with Lewy Bodies. αSyn is hypothesized to misfold and spread throughout the brain in a prion-like fashion. Transmission of αsyn necessitates the release of misfolded αsyn from one cell and the uptake of that αsyn by another, in which it can template the misfolding of endogenous αsyn upon cell internalization.