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Hippocampal Versus Cortical Deletion Of Cholinergic Receptor Muscarinic 1 In Mice Differentially Affects Post-Translational Modifications And Supramolecular Assembly Of Respiratory Chain-Associated Proteins, Mitochondrial Ultrastructure, And Respiration: Implications In Alzheimer's Disease, Mohammad Golam Sabbir, Mamiko Swanson, Robert C. Speth, Benedict C. Albensi
Hippocampal Versus Cortical Deletion Of Cholinergic Receptor Muscarinic 1 In Mice Differentially Affects Post-Translational Modifications And Supramolecular Assembly Of Respiratory Chain-Associated Proteins, Mitochondrial Ultrastructure, And Respiration: Implications In Alzheimer's Disease, Mohammad Golam Sabbir, Mamiko Swanson, Robert C. Speth, Benedict C. Albensi
HPD Articles
In a previous retrospective study using postmortem human brain tissues, we demonstrated that loss of Cholinergic Receptor Muscarinic 1 (CHRM1) in the temporal cortex of a subset of Alzheimer's patients was associated with poor survival, whereas similar loss in the hippocampus showed no such association. Mitochondrial dysfunction underlies Alzheimer's pathogenesis. Therefore, to investigate the mechanistic basis of our findings, we evaluated cortical mitochondrial phenotypes in Chrm1 knockout (Chrm1) mice. Cortical Chrm1 loss resulted in reduced respiration, reduced supramolecular assembly of respiratory protein complexes, and caused mitochondrial ultrastructural abnormalities. These mouse-based findings mechanistically linked cortical CHRM1 loss with poor survival of …