Variants of leucine-rich repeat kinase 2 (lrrk2) are associated with an increased risk in developing Parkinson’s disease (PD). Mitochondrial dysfunction and specifically mitochondrial Ca2+ handling has been linked to the pathogenesis of PD. Here we describe for the second time a mitochondrial Ca2+ efflux deficiency in a model displaying alterations in a PD-associated risk protein. LRRK2 deletion, inhibition and mutations led to an impaired mitochondrial Ca2+ extrusion via Na+/Ca2+/Li+ exchanger (NCLX) which in turn lowered mitochondrial permeability transition pore (PTP) opening threshold and increased cell death. The mitochondrial membrane potential was found not to be the underlying cause for the Ca2+ extrusion deficiency. NCLX activity was rescued by a direct (phosphomimetic NCLX mutant) and indirect (protein kinase A) activation which in turn elevated the PTP opening threshold. Therefore, at least two PD-associated risk protein pathways appear to converge on NCLX controlling mitochondrial Ca2+ extrusion and therefore mitochondrial health. Since mitochondrial Ca2+ overload has been described in many neurological disorders this study warrants further studies into NCLX as a potential therapeutic target.

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Although nearly two decades have passed since the Honey Report was issued, MPA education is still wrestling with the “relevance question.” This exploratory study seeks to assess the relevance issue from the unique vantage point of 183 mid-career MPA students at sixteen universities across the country. Queried are mid-careerist perceptions of the content, effect, and curriculum development needs of their MPA educational experience. The findings indicate: (1) a concern about the theoretical versus practical application focus of the mid-careerist experience; (2) a perception by these students that MPA education was having a substantial effect on their work habits, attitudes, and values; (3) a feeling that the balance afforded to ethics, politics, and skill development should probably differ among the subdisciplines; (4) a convergence of opinion with pre-service students on the most appropriate teaching styles for PA classrooms; (5) the perception that distinct differences existed in pre-service/mid-careerists to help academics provide a more applied view of the public service to pre-service students. The study concludes by arguing for the adoption of a service delivery ethic stressing knowledge co—production in the MPA educational process.