biostudies-literatureCroft CLAlzheimer's Research UK (ARUK)U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)173https://www.ebi.ac.uk/biostudies/studies/S-EPMC9763367biostudies-literatureUnknown8(1)The accumulation of α-synuclein (α-syn) in intracellular formations known as Lewy bodies (LBs) is associated with several neurodegenerative diseases including Parkinson's disease and Lewy Body Dementia. There is still limited understanding of how α-syn and LB formation is associated with cellular dysfunction and degeneration in these diseases. To examine the clearance and production dynamics of α-syn we transduced organotypic murine brain slice cultures (BSCs) with recombinant adeno-associated viruses (rAAVs) to express Dendra2-tagged human wild-type (WT) and mutant A53T α-syn, with and without the addition of exogenous α-syn fibrillar seeds and tracked them over several weeks in culture using optical pulse labeling. We found that neurons expressing WT or mutant A53T human α-syn show similNPJ Parkinson's diseaseOptical pulse labeling studies reveal exogenous seeding slows α-synuclein clearance.PMC9763367U01AG046139U01TR003715ARUK-RADF2019A-003Goodwin MSMoran CAPaterno GCruz PEGiasson BICroft CLRyu DHVause ARRowe LAGolde TEfalseOptical pulse labeling studies reveal exogenous seeding slows α-synuclein clearance.The accumulation of α-synuclein (α-syn) in intracellular formations known as Lewy bodies (LBs) is associated with several neurodegenerative diseases including Parkinson's disease and Lewy Body Dementia. There is still limited understanding of how α-syn and LB formation is associated with cellular dysfunction and degeneration in these diseases. To examine the clearance and production dynamics of α-syn we transduced organotypic murine brain slice cultures (BSCs) with recombinant adeno-associated viruses (rAAVs) to express Dendra2-tagged human wild-type (WT) and mutant A53T α-syn, with and without the addition of exogenous α-syn fibrillar seeds and tracked them over several weeks in culture using optical pulse labeling. We found that neurons expressing WT or mutant A53T human α-syn show simil2022-01-01T00:00:00Z2022 Dec2025-04-26T09:49:07.388Z2025-04-06T13:08:22.064ZS-EPMC97633673653595310.1038/s41531-022-00434-4