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Full-Text Articles in Medicine and Health Sciences
Perturbed Mitochondria-Er Contacts In Live Neurons That Model The Amyloid Pathology Of Alzheimer's Disease., Pamela V. Martino Adami, Zuzana Nichtova, David B. Weaver, Adam Bartok Dr., Thomas Wisniewski, Drew R. Jones, Sonia Do Carmo, Eduardo M. Castaño, A. Claudio Cuello, György Hajnóczky, Laura Morelli
Perturbed Mitochondria-Er Contacts In Live Neurons That Model The Amyloid Pathology Of Alzheimer's Disease., Pamela V. Martino Adami, Zuzana Nichtova, David B. Weaver, Adam Bartok Dr., Thomas Wisniewski, Drew R. Jones, Sonia Do Carmo, Eduardo M. Castaño, A. Claudio Cuello, György Hajnóczky, Laura Morelli
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
The use of fixed fibroblasts from familial and sporadic Alzheimer's disease patients has previously indicated an upregulation of mitochondria-ER contacts (MERCs) as a hallmark of Alzheimer's disease. Despite its potential significance, the relevance of these results is limited because they were not extended to live neurons. Here we performed a dynamic in vivo analysis of MERCs in hippocampal neurons from McGill-R-Thy1-APP transgenic rats, a model of Alzheimer's disease-like amyloid pathology. Live FRET imaging of neurons from transgenic rats revealed perturbed 'lipid-MERCs' (gap width <10 nm), while 'Ca2+-MERCs' (10-20 nm gap width) were unchanged. In situ TEM showed no significant differences in the lipid-MERCs:total MERCs or lipid-MERCs:mitochondria ratios; however, the average length of lipid-MERCs was significantly decreased in neurons from transgenic rats as compared to controls. In accordance with FRET results, untargeted lipidomics showed significant decreases in levels of 12 lipids and bioenergetic analysis revealed respiratory dysfunction of mitochondria from transgenic rats. Thus, our results reveal changes in MERC structures coupled with impaired mitochondrial functions in Alzheimer's disease-related neurons.This article has an associated First Person interview with the first author of the paper.
Gangliosides: Treatment Avenues In Neurodegenerative Disease., Pierre J. Magistretti, Fred H. Geisler, Jay S. Schneider, P. Andy Li, Hubert Fiumelli, Simonetta Sipione
Gangliosides: Treatment Avenues In Neurodegenerative Disease., Pierre J. Magistretti, Fred H. Geisler, Jay S. Schneider, P. Andy Li, Hubert Fiumelli, Simonetta Sipione
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Gangliosides are cell membrane components, most abundantly in the central nervous system (CNS) where they exert among others neuro-protective and -restorative functions. Clinical development of ganglioside replacement therapy for several neurodegenerative diseases was impeded by the BSE crisis in Europe during the 1990s. Nowadays, gangliosides are produced bovine-free and new pre-clinical and clinical data justify a reevaluation of their therapeutic potential in neurodegenerative diseases. Clinical experience is greatest with monosialo-tetrahexosyl-ganglioside (GM1) in the treatment of stroke. Fourteen randomized controlled trials (RCTs) in overall >2,000 patients revealed no difference in survival, but consistently superior neurological outcomes vs. placebo. GM1 was shown …