biostudies-literatureFleming SMUC Gardner Family Center for Parkinson’s Disease and Movement DisordersNINDS NIH HHSNational Institutes of HealthUniversity of Cincinnati Neuroscience Institute256-266https://www.ebi.ac.uk/biostudies/studies/S-EPMC10178982biostudies-literatureUnknown64Loss of function mutations in the P₅-ATPase ATP13A2 are associated with Kufor-Rakeb Syndrome and Neuronal Ceroid Lipofuscinosis. While the function of ATP13A2 is unclear, in vitro studies suggest it is a lysosomal protein that interacts with the metals manganese (Mn) and zinc and the presynaptic protein alpha-synuclein. Loss of ATP13A2 function in mice causes sensorimotor deficits, enhanced autofluorescent storage material, and accumulation of alpha-synuclein. The present study sought to determine the effect of Mn administration on these same outcomes in ATP13A2-deficient mice. Wildtype and ATP13A2-deficient mice received saline or Mn at 5-9 or 12-19 months for 45days. Sensorimotor function was assessed starting at day 30. Autofluorescence was quantified in multiple brain regionNeurotoxicologyThe effect of manganese exposure in Atp13a2-deficient mice.PMC10178982NS070268R15 NS070268R21 NS077022NS077022Schultheis PJSantiago NALemkuhl ALiou BShull GEPamphile SSun YEkhator ORLinn SCAga DSHolden JGFleming SMMullin EJRoth JAKarkare SfalseThe effect of manganese exposure in Atp13a2-deficient mice.Loss of function mutations in the P₅-ATPase ATP13A2 are associated with Kufor-Rakeb Syndrome and Neuronal Ceroid Lipofuscinosis. While the function of ATP13A2 is unclear, in vitro studies suggest it is a lysosomal protein that interacts with the metals manganese (Mn) and zinc and the presynaptic protein alpha-synuclein. Loss of ATP13A2 function in mice causes sensorimotor deficits, enhanced autofluorescent storage material, and accumulation of alpha-synuclein. The present study sought to determine the effect of Mn administration on these same outcomes in ATP13A2-deficient mice. Wildtype and ATP13A2-deficient mice received saline or Mn at 5-9 or 12-19 months for 45days. Sensorimotor function was assessed starting at day 30. Autofluorescence was quantified in multiple brain region2018-01-01T00:00:00Z2018 Jan2025-04-26T14:23:46.466Z2025-04-06T14:36:49.826ZS-EPMC101789822859591210.1016/j.neuro.2017.06.005