The distribution of tau in the mammalian central nervous system.

Binder, Lester I.; Frankfurter, Anthony; Rebhun, Lionel I.

doi:10.1083/jcb.101.4.1371

Cited by 1,467 publications

(954 citation statements)

References 45 publications

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“…In the sham-operated rats, the pattern of T-l im munoreactivity was consistent with the axonal lo calization described previously (Binder et al, 1985). The neuropil was intensely stained and neu ronal perikarya and dendrites were immunonega tive.…”

Section: -1supporting

confidence: 88%

Alterations in τ Immunostaining in the Rat Hippocampus following Transient Cerebral Ischemia

Geddes¹,

Schwab²,

Craddock³

et al. 1994

J Cereb Blood Flow Metab

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Summary: Previous studies in gerbils have shown that cytoskeletal disruption and a loss of the dendritic micro tubule-associated protein, MAP2, may occur after short periods of transient global ischemia. T, a predominantly axonal microtubule-associated protein, has not been ex amined following ischemia. We compared neuronal dam age with alterations in MAP2, T, and 72-kD heat shock protein (HSP72) immunostaining at various reperfusion times following 20 min of ischemia in the rat four-vessel occlusion model. T accumulated in neuronal cell bodies throughout the hippocampal formation 30 min to 2 h after the ischemic insult. Perikaryal T immunostaining was transient in most regions, but persisted in polymorphic hilar neurons. This was accompanied by a loss of immu no staining in the target of many hilar neurons, the inner Transient global ischemia is followed by a de layed loss of neurons in select brain regions, includ ing the hippocampus (for review see Schmidt Kastner and Freund, 1991). Using the rat four vessel occlusion model (Pulsinelli and Brierly, 1979), ischemia maintained for 20 min in halothane anesthetized animals results in neuronal damage in CAl and hilus, but not in CA3 (Jorgensen and Di emer, 1982; Pulsinelli et aI., 1982). The postisch emic rate of cell death is not uniform, with hilar neurons degenerating within a few hours, but CAl pyramidal cells degenerating 24-72 h following isch emia and reperfusion (Crain et aI., 1988; Hsu and Received August 3, 1993; final revision received October 28, 1993; accepted November 23, 1993. Address correspondence and reprint requests to Dr. James W. Geddes, 209 Sanders-Brown Building, University of Kentucky, Lexington, KY 40536-0230, U. S. A.Abbreviations used : HSP, heat shock protein; KA, kainic acid; MAP, microtubule-associated protein; TBS, Tris-buffered saline; 4VO, four-vessel occlusion. 554 molecular layer of the dentate gyrus. The same neuronal populations that exhibited increased T immunostaining of perikarya later displayed an induction of HSP72 immu noreactivity. In contrast, loss of MAP2 immunostaining was not consistently observed before neuronal death and did not correspond to HSP72 induction. The altered T immunostaining is not the direct result of excitotoxic in sult, as intrahippocampal injection of kainic acid did not cause the somal accumulation of T, but did cause disrup tion of MAP2 immunostaining. Taken together, the re sults suggest that the somal accumulation of T is an early, sensitive, and selective marker of ischemic insult.

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Section: -1supporting

confidence: 88%

Alterations in τ Immunostaining in the Rat Hippocampus following Transient Cerebral Ischemia

Geddes¹,

Schwab²,

Craddock³

et al. 1994

J Cereb Blood Flow Metab

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“…Tau, which is preferentially found in axons (Binder et al, 1985), and MAP2, which is preferentially found in dendrites (Bernhardt and Matus, 1984), might bundle MTs because overexpression of these proteins in insect cells generates processes that have MT-MT spacings that reflect the size of the MAP (Chen et al, 1992). Nonetheless, mice lacking either tau or MAP2 have relatively normal neurons, which suggests that other factors are involved (Harada et al, 1994;Teng et al, 2001).…”

Section: Mt Bundlingmentioning

confidence: 98%

Generation of noncentrosomal microtubule arrays

Bartolini

Gundersen

2006

Journal of Cell Science

226

219

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In most proliferating and migrating animal cells, the centrosome is the main site for microtubule (MT) nucleation and anchoring, leading to the formation of radial MT arrays in which MT minus ends are anchored at the centrosomes and plus ends extend to the cell periphery. By contrast, in most differentiated animal cell types, including muscle, epithelial and neuronal cells, as well as most fungi and vascular plant cells, MTs are arranged in noncentrosomal arrays that are non-radial. Recent studies suggest that these noncentrosomal MT arrays are generated by a three step process. The initial step involves formation of noncentrosomal MTs by distinct mechanisms depending on cell type: release from the centrosome, catalyzed nucleation at noncentrosomal sites or breakage of pre-existing MTs. The second step involves transport by MT motor proteins or treadmilling to sites of assembly. In the final step, the noncentrosomal MTs are rearranged into cell-type-specific arrays by bundling and/or capture at cortical sites, during which MTs acquire stability. Despite their relative stability, the final noncentrosomal MT arrays may still exhibit dynamic properties and in many cases can be remodeled.

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“…1,2 The synthesis of tau is upregulated along with tubulin during neuronal differentiation; in mature neurons, tau occurs mostly in the axon and is largely excluded from the somatodendritic compartment, whereas other MAPs (e.g., MAP2) predominate in dendrites. 3,4 Microtubules must be able to dynamically grow and shrink, to support cellular shape changes. This is a prerequisite to establishing neuronal polarity and axonal outgrowth.…”

Section: Cell Biology and Function Of Taumentioning

confidence: 99%

Tau-Based Treatment Strategies in Neurodegenerative Diseases

2008

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Summary:Neurofibrillary tangles are a characteristic hallmark of Alzheimer's and other neurodegenerative diseases, such as Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). These diseases are summarized as tauopathies, because neurofibrillary tangles are composed of intracellular aggregates of the microtubule-associated protein tau. The molecular mechanisms of tau-mediated neurotoxicity are not well understood; however, pathologic hyperphosphorylation and aggregation of tau play a central role in neurodegeneration and neuronal dysfunction. The present review, therefore, focuses on therapeutic approaches that aim to inhibit tau phosphorylation and aggregation or to dissolve preexisting tau aggregates. Further experimental therapy strategies include the enhancement of tau clearance by activation of proteolytic, proteasomal, or autophagosomal degradation pathways or anti-tau directed immunotherapy. Hyperphosphorylated tau does not bind microtubules, leading to microtubule instability and transport impairment. Pharmacological stabilization of microtubule networks might counteract this effect. In several tauopathies there is a shift toward four-repeat tau isoforms, and interference with the splicing machinery to decrease four-repeat splicing might be another therapeutic option.

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The distribution of tau in the mammalian central nervous system.

Cited by 1,467 publications

References 45 publications

Alterations in τ Immunostaining in the Rat Hippocampus following Transient Cerebral Ischemia

Alterations in τ Immunostaining in the Rat Hippocampus following Transient Cerebral Ischemia

Generation of noncentrosomal microtubule arrays

Tau-Based Treatment Strategies in Neurodegenerative Diseases

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