Learn More
Frontotemporal dementia (FTD) is characterized by cognitive and behavioral changes and, in a significant subset of patients, Parkinsonism. Histopathologically, FTD frequently presents with tau-containing lesions, which in familial cases result from mutations in the MAPT gene encoding tau. Here we present a novel transgenic mouse strain (K3) that expresses(More)
Primary cultures of rat and murine hippocampal neurons are widely used to reveal cellular mechanisms in neurobiology. Their use is limited, as culturing at low density is often not possible or is dependent on sophisticated methods. Here we present a novel method for culturing embryonic (E16.5) murine hippocampal neurons, using a spatially separated ring of(More)
Abnormal tau-immunoreactive filaments are a hallmark of tauopathies, including Alzheimer's disease (AD). A higher phosphorylation ("hyperphosphorylation") state of tau protein may represent a critical event. To determine the potential role of tau hyperphosphorylation in these disorders, mutated tau proteins were produced where serine/threonine residues(More)
The actin cytoskeleton is a potentially vulnerable property of cancer cells, yet chemotherapeutic targeting attempts have been hampered by unacceptable toxicity. In this study, we have shown that it is possible to disrupt specific actin filament populations by targeting isoforms of tropomyosin, a core component of actin filaments, that are selectively(More)
The existence of a feedback mechanism regulating the precise amounts of muscle structural proteins, such as actin and the actin-associated protein tropomyosin (Tm), in the sarcomeres of striated muscles is well established. However, the regulation of nonmuscle or cytoskeletal actin and Tms in nonmuscle cell structures has not been elucidated. Unlike the(More)
The role of hyperphosphorylation of tau in Alzheimer's disease is still unsolved. Here we describe a novel transgenic mouse model, expressing a pseudohyperphosphorylated (PHP) variant of the longest human CNS tau isoform in forebrain neurons. We report that pseudohyperphosphorylation decreases phosphorylation at T205 while other sites (T212, S262) are less(More)
The establishment of axonal-somatodendritic polarity is an important event during neuronal development. The analysis of the underlying molecular events requires experimental models that display characteristic steps in the development of polarity and that are accessible for experimental manipulations. Here we show that human model neurons (NT2-N cells) can(More)
Aggregation and increased phosphorylation of tau at selected sites ("hyperphosphorylation") are histopathological hallmarks of Alzheimer's disease (AD). However, it is not known whether the tau pathology has a primary role during neuronal degeneration. To determine the role of tau hyperphosphorylation in AD, pseudohyperphosphorylated tau (PHP-tau) that(More)
The microtubule-associated tau proteins represent a family of closely related phosphoproteins that become enriched in the axons during brain development. In Alzheimer's disease (AD), tau aggregates somatodendritically in paired helical filaments in a hyperphosphorylated form. Most of the sites that are phosphorylated to a high extent in paired helical(More)
The microtubule-associated tau proteins become functionally and structurally altered in Alzheimer's disease (AD). To analyze tau modification and its role in a non-vertebrate animal model, we produced transgenic Caenorhabditis elegans strains with a panneuronal expression of human tau and a pseudohyperphosphorylated (PHP) tau construct that mimics(More)