Neurobiology of Disease Pathogenic Forms of Tau Inhibit Kinesin-Dependent Axonal Transport through a Mechanism Involving Activation of Axonal Phosphotransferases
نویسندگان
چکیده
Nicholas M. Kanaan,1,2,3 Gerardo A. Morfini,3,4* Nichole E. LaPointe,3,5 Gustavo F. Pigino,3,4 Kristina R. Patterson,1,3 Yuyu Song,3,4 Athena Andreadis,6 Yifan Fu,1 Scott T. Brady,3,4* and Lester I. Binder1* 1Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, 2Division of Translational Science and Molecular Medicine, College of Human Medicine, Michigan State University, Grand Rapids, Michigan 49503, 3Marine Biological Laboratory, Woods Hole, Massachusetts 02543, 4Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, Illinois 60612, 5Neuroscience Research Institute, University of California, Santa Barbara, California 93106, and 6Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655
منابع مشابه
Pathogenic forms of tau inhibit kinesin-dependent axonal transport through a mechanism involving activation of axonal phosphotransferases.
Aggregated filamentous forms of hyperphosphorylated tau (a microtubule-associated protein) represent pathological hallmarks of Alzheimer's disease (AD) and other tauopathies. While axonal transport dysfunction is thought to represent a primary pathogenic factor in AD and other neurodegenerative diseases, the direct molecular link between pathogenic forms of tau and deficits in axonal transport ...
متن کاملSubcellular trafficking of the amyloid precursor protein gene family and its pathogenic role in Alzheimer's disease.
Changes in the intracellular transport of amyloid precursor protein (APP) affect the extent to which APP is exposed to alpha- or beta-secretase in a common subcellular compartment and therefore directly influence the degree to which APP undergoes the amyloidogenic pathway leading to generation of beta-amyloid. As the presynaptic regions of neurons are thought to be the main source of beta-amylo...
متن کاملThe amino terminus of tau inhibits kinesin-dependent axonal transport: implications for filament toxicity.
The neuropathology of Alzheimer's disease (AD) and other tauopathies is characterized by filamentous deposits of the microtubule-associated protein tau, but the relationship between tau polymerization and neurotoxicity is unknown. Here, we examined effects of filamentous tau on fast axonal transport (FAT) using isolated squid axoplasm. Monomeric and filamentous forms of recombinant human tau we...
متن کاملAxonal stress kinase activation and tau misbehavior induced by kinesin-1 transport defects.
Many neurodegenerative diseases exhibit axonal pathology, transport defects, and aberrant phosphorylation and aggregation of the microtubule binding protein tau. While mutant tau protein in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP17) causes aberrant microtubule binding and assembly of tau into filaments, the pathways leading to tau-mediated neurotoxicity in Alzheim...
متن کاملKinesin-1 transport reductions enhance human tau hyperphosphorylation, aggregation and neurodegeneration in animal models of tauopathies.
Neurodegeneration induced by abnormal hyperphosphorylation and aggregation of the microtubule-associated protein tau defines neurodegenerative tauopathies. Destabilization of microtubules by loss of tau function and filament formation by toxic gain of function are two mechanisms suggested for how abnormal tau triggers neuronal loss. Recent experiments in kinesin-1 deficient mice suggested that ...
متن کامل