Synaptotoxicity in Alzheimer's Disease Involved a Dysregulation of Actin Cytoskeleton Dynamics through Cofilin 1 Phosphorylation

• Published in: The Journal of neuroscience Vol. 38; no. 48; pp. 10349 - 10361
• Main Authors: Rush, Travis, Martinez-Hernandez, Jose, Dollmeyer, Marc, Frandemiche, Marie Lise, Borel, Eve, Boisseau, Sylvie, Jacquier-Sarlin, Muriel, Buisson, Alain
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 28.11.2018
• Subjects: Actin; Actins - metabolism; Adult; Aged; Aged, 80 and over; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid; Animals; Calcium; Calcium imaging; Cells, Cultured; Cofilin; Cofilin 1 - metabolism; Cognitive ability; Cytoskeleton; Cytoskeleton - metabolism; Cytoskeleton - pathology; Dendritic plasticity; Dendritic spines; Dendritic structure; Female; Fluorescence; Fluorescence recovery after photobleaching; Humans; Impairment; Inhibitors; Kinases; Long-term potentiation; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Middle Aged; Molecular modelling; Mutants; Neurodegenerative diseases; Neurons; Oligomers; Pathophysiology; Patients; Phosphorylation; Phosphorylation - physiology; Photobleaching; Postsynaptic density; Presenilin 1; Protein kinase; Proteins; Rocks; Rods; Spine; Stabilization; Synapses; Synapses - metabolism; Synapses - pathology; Synaptic plasticity; Synaptic strength; Synaptosomes; Therapeutic applications; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors; actin; cofilin; amyloid-β oligomers; Alzheimer's disease; fasudil; Rho-associated protein

Amyloid-β (Aβ) drives the synaptic impairment and dendritic spine loss characteristic of Alzheimer's disease (AD), but how Aβ affects the actin cytoskeleton remains unknown and contentious. The actin-binding protein, cofilin-1 (cof1), is a major regulator of actin dynamics in dendritic spines,...