De novo actin polymerization is required for model Hirano body formation in Dictyostelium.

Hirano bodies are eosinophilic, actin-rich inclusions found in autopsied brains in numerous neurodegenerative diseases. The mechanism of Hirano body formation is unknown. Mass spectrometry analysis was performed to identify proteins from partially purified model Hirano bodies from Dictyostelium This analysis identified proteins primarily belonging to ribosomes, proteasomes, mitochondria and cytoskeleton.

Alterations in synaptic plasticity coincide with deficits in spatial working memory in presymptomatic 3xTg-AD mice.

Alzheimer's disease is a neurodegenerative condition believed to be initiated by production of amyloid-beta peptide, which leads to synaptic dysfunction and progressive memory loss. Using a mouse model of Alzheimer's disease (3xTg-AD), an 8-arm radial maze was employed to assess spatial working memory. Unexpectedly, the younger (3month old) 3xTg-AD mice were as impaired in the spatial working memory task as the older (8month old) 3xTg-AD mice when compared with age-matched NonTg control animals.

Hirano body expression impairs spatial working memory in a novel mouse model.

Introduction: Hirano bodies are actin-rich intracellular inclusions found in the brains of patients with neurodegenerative conditions such as Alzheimer's disease or frontotemporal lobar degeneration-tau. While Hirano body ultrastructure and protein composition have been well studied, little is known about the physiological function of Hirano bodies in an animal model system.

Results: Utilizing a Cre/Lox system, we have generated a new mouse model which develops an age-dependent increase in the number of model Hirano bodies present in both the CA1 region of the hippocampus and frontal cortex.

Hirano bodies differentially modulate cell death induced by tau and the amyloid precursor protein intracellular domain.

Background: Hirano bodies are actin-rich paracrystalline inclusions found in brains of patients with Alzheimer's disease (AD), frontotemporal dementia (FTD), and in normal aged individuals. Although studies of post-mortem brain tissue provide clues of etiology, the physiological function of Hirano bodies remains unknown. A cell culture model was utilized to study the interactions of mutant tau proteins, model Hirano bodies, and GSK3β in human astrocytoma cells.

Requirements for Hirano body formation.

Hirano bodies are paracrystalline F-actin-rich structures associated with diverse conditions, including neurodegeneration and aging. Generation of model Hirano bodies using altered forms of Dictyostelium 34-kDa actin-bundling protein allows studies of their physiological function and mechanism of formation. We describe a novel 34-kDa protein mutant, E60K, with a point mutation within the inhibitory domain of the 34-kDa protein.