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P4‐514: TRACKING ENLARGED PERIVASCULAR SPACES FROM CLINICAL MRI TO POST‐MORTEM MRI GUIDED HISTOPATHOLOGY
Author(s) -
Boespflug Erin L.,
Lahna David,
Woltjer Randall L.,
Schwartz Daniel,
Roese Natalie,
Grinstead John,
Kaye Jeffrey A.,
Rooney William D.,
Silbert Lisa
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.08.060
Subject(s) - perivascular space , magnetic resonance imaging , medicine , histopathology , white matter , pathology , anatomy , nuclear medicine , radiology
still being debated. Now, we purified and reconstituted monomeric ATP synthase from porcine heart mitochondria into small unilamellar lipid vesicles (SUVs) and analyzed its oligomeric state by single-particle electron cryomicroscopy. Results: Here, we present the cryo-EM structure of functionally active monomeric ATP synthase in SUVs at w16 A resolution. The patch-clamp recordings reveal that this preparation of SUV-reconstituted ATP synthase monomers, when fused into giant unilamellar vesicles (GUVs), form voltage-gated and Ca-activated channels with the key features of mPTP. Conclusions: Based on our findings we conclude that the ATP synthase monomer is sufficient, and dimer formation is not required for its megachannel activity. In-depth structural analysis of ATP synthase will reveal its “open channel” conformation and will lead to a structure-based drug design of specific therapeutic compounds for the treatment of Alzheimer’s disease and other neurological disorders.