The Experts below are selected from a list of 36 Experts worldwide ranked by ideXlab platform
Claire Goldsbury - One of the best experts on this subject based on the ideXlab platform.
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activated actin depolymerizing factor cofilin sequesters phosphorylated microtubule associated protein during the assembly of alzheimer like neuritic cytoskeletal striations
The Journal of Neuroscience, 2009Co-Authors: Ineka T Whiteman, Othon L Gervasio, Karen M Cullen, Gilles J Guillemin, Erica V Jeong, Paul K Witting, Shane T Antao, Laurie S Minamide, James R Bamburg, Claire GoldsburyAbstract:In Alzheimer9s disease (AD), rod-like cofilin aggregates (cofilin–actin rods) and Thread-like inclusions containing phosphorylated microtubule-associated protein (pMAP) tau form in the brain (Neuropil Threads), and the extent of their presence correlates with cognitive decline and disease progression. The assembly mechanism of these respective pathological lesions and the relationship between them is poorly understood, yet vital to understanding the causes of sporadic AD. We demonstrate that, during mitochondrial inhibition, activated actin-depolymerizing factor (ADF)/cofilin assemble into rods along processes of cultured primary neurons that recruit pMAP/tau and mimic Neuropil Threads. Fluorescence resonance energy transfer analysis revealed colocalization of cofilin-GFP (green fluorescent protein) and pMAP in rods, suggesting their close proximity within a cytoskeletal inclusion complex. The relationship between pMAP and cofilin–actin rods was further investigated using actin-modifying drugs and small interfering RNA knockdown of ADF/cofilin in primary neurons. The results suggest that activation of ADF/cofilin and generation of cofilin–actin rods is required for the subsequent recruitment of pMAP into the inclusions. Additionally, we were able to induce the formation of pMAP-positive ADF/cofilin rods by exposing cells to exogenous amyloid-β (Aβ) peptides. These results reveal a common pathway for pMAP and cofilin accumulation in neuronal processes. The requirement of activated ADF/cofilin for the sequestration of pMAP suggests that Neuropil Thread structures in the AD brain may be initiated by elevated cofilin activation and F-actin bundling that can be caused by oxidative stress, mitochondrial dysfunction, or Aβ peptides, all suspected initiators of synaptic loss and neurodegeneration in AD.
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Activated Actin-Depolymerizing Factor/Cofilin Sequesters Phosphorylated Microtubule-Associated Protein during the Assembly of Alzheimer-Like Neuritic Cytoskeletal Striations
The Journal of Neuroscience, 2009Co-Authors: Ineka T Whiteman, Othon L Gervasio, Karen M Cullen, Gilles J Guillemin, Erica V Jeong, Paul K Witting, Shane T Antao, Laurie S Minamide, James R Bamburg, Claire GoldsburyAbstract:In Alzheimer's disease (AD), rod-like cofilin aggregates (cofilin–actin rods) and Thread-like inclusions containing phosphorylated microtubule-associated protein (pMAP) tau form in the brain (Neuropil Threads), and the extent of their presence correlates with cognitive decline and disease progression. The assembly mechanism of these respective pathological lesions and the relationship between them is poorly understood, yet vital to understanding the causes of sporadic AD. We demonstrate that, during mitochondrial inhibition, activated actin-depolymerizing factor (ADF)/cofilin assemble into rods along processes of cultured primary neurons that recruit pMAP/tau and mimic Neuropil Threads. Fluorescence resonance energy transfer analysis revealed colocalization of cofilin-GFP (green fluorescent protein) and pMAP in rods, suggesting their close proximity within a cytoskeletal inclusion complex. The relationship between pMAP and cofilin–actin rods was further investigated using actin-modifying drugs and small interfering RNA knockdown of ADF/cofilin in primary neurons. The results suggest that activation of ADF/cofilin and generation of cofilin–actin rods is required for the subsequent recruitment of pMAP into the inclusions. Additionally, we were able to induce the formation of pMAP-positive ADF/cofilin rods by exposing cells to exogenous amyloid-β (Aβ) peptides. These results reveal a common pathway for pMAP and cofilin accumulation in neuronal processes. The requirement of activated ADF/cofilin for the sequestration of pMAP suggests that Neuropil Thread structures in the AD brain may be initiated by elevated cofilin activation and F-actin bundling that can be caused by oxidative stress, mitochondrial dysfunction, or Aβ peptides, all suspected initiators of synaptic loss and neurodegeneration in AD.
Ineka T Whiteman - One of the best experts on this subject based on the ideXlab platform.
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activated actin depolymerizing factor cofilin sequesters phosphorylated microtubule associated protein during the assembly of alzheimer like neuritic cytoskeletal striations
The Journal of Neuroscience, 2009Co-Authors: Ineka T Whiteman, Othon L Gervasio, Karen M Cullen, Gilles J Guillemin, Erica V Jeong, Paul K Witting, Shane T Antao, Laurie S Minamide, James R Bamburg, Claire GoldsburyAbstract:In Alzheimer9s disease (AD), rod-like cofilin aggregates (cofilin–actin rods) and Thread-like inclusions containing phosphorylated microtubule-associated protein (pMAP) tau form in the brain (Neuropil Threads), and the extent of their presence correlates with cognitive decline and disease progression. The assembly mechanism of these respective pathological lesions and the relationship between them is poorly understood, yet vital to understanding the causes of sporadic AD. We demonstrate that, during mitochondrial inhibition, activated actin-depolymerizing factor (ADF)/cofilin assemble into rods along processes of cultured primary neurons that recruit pMAP/tau and mimic Neuropil Threads. Fluorescence resonance energy transfer analysis revealed colocalization of cofilin-GFP (green fluorescent protein) and pMAP in rods, suggesting their close proximity within a cytoskeletal inclusion complex. The relationship between pMAP and cofilin–actin rods was further investigated using actin-modifying drugs and small interfering RNA knockdown of ADF/cofilin in primary neurons. The results suggest that activation of ADF/cofilin and generation of cofilin–actin rods is required for the subsequent recruitment of pMAP into the inclusions. Additionally, we were able to induce the formation of pMAP-positive ADF/cofilin rods by exposing cells to exogenous amyloid-β (Aβ) peptides. These results reveal a common pathway for pMAP and cofilin accumulation in neuronal processes. The requirement of activated ADF/cofilin for the sequestration of pMAP suggests that Neuropil Thread structures in the AD brain may be initiated by elevated cofilin activation and F-actin bundling that can be caused by oxidative stress, mitochondrial dysfunction, or Aβ peptides, all suspected initiators of synaptic loss and neurodegeneration in AD.
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Activated Actin-Depolymerizing Factor/Cofilin Sequesters Phosphorylated Microtubule-Associated Protein during the Assembly of Alzheimer-Like Neuritic Cytoskeletal Striations
The Journal of Neuroscience, 2009Co-Authors: Ineka T Whiteman, Othon L Gervasio, Karen M Cullen, Gilles J Guillemin, Erica V Jeong, Paul K Witting, Shane T Antao, Laurie S Minamide, James R Bamburg, Claire GoldsburyAbstract:In Alzheimer's disease (AD), rod-like cofilin aggregates (cofilin–actin rods) and Thread-like inclusions containing phosphorylated microtubule-associated protein (pMAP) tau form in the brain (Neuropil Threads), and the extent of their presence correlates with cognitive decline and disease progression. The assembly mechanism of these respective pathological lesions and the relationship between them is poorly understood, yet vital to understanding the causes of sporadic AD. We demonstrate that, during mitochondrial inhibition, activated actin-depolymerizing factor (ADF)/cofilin assemble into rods along processes of cultured primary neurons that recruit pMAP/tau and mimic Neuropil Threads. Fluorescence resonance energy transfer analysis revealed colocalization of cofilin-GFP (green fluorescent protein) and pMAP in rods, suggesting their close proximity within a cytoskeletal inclusion complex. The relationship between pMAP and cofilin–actin rods was further investigated using actin-modifying drugs and small interfering RNA knockdown of ADF/cofilin in primary neurons. The results suggest that activation of ADF/cofilin and generation of cofilin–actin rods is required for the subsequent recruitment of pMAP into the inclusions. Additionally, we were able to induce the formation of pMAP-positive ADF/cofilin rods by exposing cells to exogenous amyloid-β (Aβ) peptides. These results reveal a common pathway for pMAP and cofilin accumulation in neuronal processes. The requirement of activated ADF/cofilin for the sequestration of pMAP suggests that Neuropil Thread structures in the AD brain may be initiated by elevated cofilin activation and F-actin bundling that can be caused by oxidative stress, mitochondrial dysfunction, or Aβ peptides, all suspected initiators of synaptic loss and neurodegeneration in AD.
Takahiko Umahara - One of the best experts on this subject based on the ideXlab platform.
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14-3-3 proteins and zeta isoform containing neurofibrillary tangles in patients with Alzheimer’s disease
Acta Neuropathologica, 2004Co-Authors: Takahiko Umahara, Toshiki Uchihara, Kuniaki Tsuchiya, Ayako Nakamura, Toshihiko Iwamoto, Kenji Ikeda, Masaru TakasakiAbstract:Immunolocalization of 14-3-3 proteins in Alzheimer’s disease (AD) brains was investigated using isoform-specific antibodies. Weak granular immunoreactivity of 14-3-3 proteins was found in neuronal cytoplasm in control subjects and AD brains. Both intracellular and extracellular neurofibrillary tangles (NFTs), as well as Neuropil Thread-like structures, were immunopositive for 14-3-3 proteins. This was corroborated by triple-fluorolabeling method visualizing paired helical filament (PHF) tau and 14-3-3 epitopes in relation to fibrillary state detected by thiazin red. Pretangle neurons (positive for PHF-tau without fibrillary structure detected by thiazin red) only contained fine granular immunoreactivity (IR) of 14-3-3, which was similarly found in unaffected neurons. Granular cytoplasmic IR of 14-3-3 proteins in pretangle neurons was not colocalized to granular tau-like IR, which suggests that participation of 14-3-3 proteins in NFT formation was restricted to its later stages. Its zeta isoform was most prominent in these NFTs, suggesting that this isoform is a major component involved in the formation of NFTs. In contrast, IR of epsilon isoform was found in the Neuropil of the hippocampus and that of sigma isoform was localized to granule cells of the dentate gyrus in AD brains, as seen in the age-matched controls. Expression of 14-3-3 proteins were found to be highly variable and dependent on their isoforms, regions and cell types. Molecular, as well as topographical, dissection of 14-3-3 proteins will provide us with an improved understanding of this molecule in normal and pathological conditions.
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demonstration of Neuropil Thread like structures in the spinal cord white matter in progressive supranuclear palsy an immunohistochemical investigation
Neuropathology, 1995Co-Authors: Takahiko Umahara, Asao Hirano, S Kato, Noriyuki ShibataAbstract:The presentation and distribution of neurofibrillary tangles (NFT), Neuropil Thread-like structures (T-LS) and smaller structures (dots) in the spinal cord of two patients with progressive supranuclear palsy (PSP) is discussed. Monoclonal antibodies to Alzheimer neurofibrillary tangles (ANT) and tau protein were used. Immunoreactive NFT were detected in the spinal cord gray matter. The number of tau-positive NFT was significantly smaller than that of NFT stained by the anti-ANT antibody. However, T-LS and dots immunolabeled by the latter were detected in the gray and white matter. Most white matter T-LS and immunoreactive dots were found in the anterior funiculus. These findings provide immunohistochemical evidence for the presence of these abnormal structures in the spinal cord white matter of patients with PSP.
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demonstration of neurofibrillary tangles and Neuropil Thread like structures in spinal cord white matter in parkinsonism dementia complex on guam and in guamanian amyotrophic lateral sclerosis
Acta Neuropathologica, 1994Co-Authors: Takahiko Umahara, Asao Hirano, S Kato, Noriyuki ShibataAbstract:This report concerns the demonstration and distribution of neurofibrillary tangles (NFTs), immunoreactive Neuropil Thread-like structures and dots in the spinal cord gray and white matter of six patients with parkinsonism-dementia complex on Guam and five patients with Guamanian amyotrophic lateral sclerosis (ALS). A monoclonal antibody to Alzheimer NFTs was used. NFTs were found in the spinal cord gray matter and white matter and all patients had immunoreactive Neuropil Thread-like structures and dots in the gray matter as well as in the white matter. They were particularly numerous in the lateral funiculus of patients with Guamanian ALS.
Noriyuki Shibata - One of the best experts on this subject based on the ideXlab platform.
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demonstration of Neuropil Thread like structures in the spinal cord white matter in progressive supranuclear palsy an immunohistochemical investigation
Neuropathology, 1995Co-Authors: Takahiko Umahara, Asao Hirano, S Kato, Noriyuki ShibataAbstract:The presentation and distribution of neurofibrillary tangles (NFT), Neuropil Thread-like structures (T-LS) and smaller structures (dots) in the spinal cord of two patients with progressive supranuclear palsy (PSP) is discussed. Monoclonal antibodies to Alzheimer neurofibrillary tangles (ANT) and tau protein were used. Immunoreactive NFT were detected in the spinal cord gray matter. The number of tau-positive NFT was significantly smaller than that of NFT stained by the anti-ANT antibody. However, T-LS and dots immunolabeled by the latter were detected in the gray and white matter. Most white matter T-LS and immunoreactive dots were found in the anterior funiculus. These findings provide immunohistochemical evidence for the presence of these abnormal structures in the spinal cord white matter of patients with PSP.
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demonstration of neurofibrillary tangles and Neuropil Thread like structures in spinal cord white matter in parkinsonism dementia complex on guam and in guamanian amyotrophic lateral sclerosis
Acta Neuropathologica, 1994Co-Authors: Takahiko Umahara, Asao Hirano, S Kato, Noriyuki ShibataAbstract:This report concerns the demonstration and distribution of neurofibrillary tangles (NFTs), immunoreactive Neuropil Thread-like structures and dots in the spinal cord gray and white matter of six patients with parkinsonism-dementia complex on Guam and five patients with Guamanian amyotrophic lateral sclerosis (ALS). A monoclonal antibody to Alzheimer NFTs was used. NFTs were found in the spinal cord gray matter and white matter and all patients had immunoreactive Neuropil Thread-like structures and dots in the gray matter as well as in the white matter. They were particularly numerous in the lateral funiculus of patients with Guamanian ALS.
Karen M Cullen - One of the best experts on this subject based on the ideXlab platform.
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activated actin depolymerizing factor cofilin sequesters phosphorylated microtubule associated protein during the assembly of alzheimer like neuritic cytoskeletal striations
The Journal of Neuroscience, 2009Co-Authors: Ineka T Whiteman, Othon L Gervasio, Karen M Cullen, Gilles J Guillemin, Erica V Jeong, Paul K Witting, Shane T Antao, Laurie S Minamide, James R Bamburg, Claire GoldsburyAbstract:In Alzheimer9s disease (AD), rod-like cofilin aggregates (cofilin–actin rods) and Thread-like inclusions containing phosphorylated microtubule-associated protein (pMAP) tau form in the brain (Neuropil Threads), and the extent of their presence correlates with cognitive decline and disease progression. The assembly mechanism of these respective pathological lesions and the relationship between them is poorly understood, yet vital to understanding the causes of sporadic AD. We demonstrate that, during mitochondrial inhibition, activated actin-depolymerizing factor (ADF)/cofilin assemble into rods along processes of cultured primary neurons that recruit pMAP/tau and mimic Neuropil Threads. Fluorescence resonance energy transfer analysis revealed colocalization of cofilin-GFP (green fluorescent protein) and pMAP in rods, suggesting their close proximity within a cytoskeletal inclusion complex. The relationship between pMAP and cofilin–actin rods was further investigated using actin-modifying drugs and small interfering RNA knockdown of ADF/cofilin in primary neurons. The results suggest that activation of ADF/cofilin and generation of cofilin–actin rods is required for the subsequent recruitment of pMAP into the inclusions. Additionally, we were able to induce the formation of pMAP-positive ADF/cofilin rods by exposing cells to exogenous amyloid-β (Aβ) peptides. These results reveal a common pathway for pMAP and cofilin accumulation in neuronal processes. The requirement of activated ADF/cofilin for the sequestration of pMAP suggests that Neuropil Thread structures in the AD brain may be initiated by elevated cofilin activation and F-actin bundling that can be caused by oxidative stress, mitochondrial dysfunction, or Aβ peptides, all suspected initiators of synaptic loss and neurodegeneration in AD.
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Activated Actin-Depolymerizing Factor/Cofilin Sequesters Phosphorylated Microtubule-Associated Protein during the Assembly of Alzheimer-Like Neuritic Cytoskeletal Striations
The Journal of Neuroscience, 2009Co-Authors: Ineka T Whiteman, Othon L Gervasio, Karen M Cullen, Gilles J Guillemin, Erica V Jeong, Paul K Witting, Shane T Antao, Laurie S Minamide, James R Bamburg, Claire GoldsburyAbstract:In Alzheimer's disease (AD), rod-like cofilin aggregates (cofilin–actin rods) and Thread-like inclusions containing phosphorylated microtubule-associated protein (pMAP) tau form in the brain (Neuropil Threads), and the extent of their presence correlates with cognitive decline and disease progression. The assembly mechanism of these respective pathological lesions and the relationship between them is poorly understood, yet vital to understanding the causes of sporadic AD. We demonstrate that, during mitochondrial inhibition, activated actin-depolymerizing factor (ADF)/cofilin assemble into rods along processes of cultured primary neurons that recruit pMAP/tau and mimic Neuropil Threads. Fluorescence resonance energy transfer analysis revealed colocalization of cofilin-GFP (green fluorescent protein) and pMAP in rods, suggesting their close proximity within a cytoskeletal inclusion complex. The relationship between pMAP and cofilin–actin rods was further investigated using actin-modifying drugs and small interfering RNA knockdown of ADF/cofilin in primary neurons. The results suggest that activation of ADF/cofilin and generation of cofilin–actin rods is required for the subsequent recruitment of pMAP into the inclusions. Additionally, we were able to induce the formation of pMAP-positive ADF/cofilin rods by exposing cells to exogenous amyloid-β (Aβ) peptides. These results reveal a common pathway for pMAP and cofilin accumulation in neuronal processes. The requirement of activated ADF/cofilin for the sequestration of pMAP suggests that Neuropil Thread structures in the AD brain may be initiated by elevated cofilin activation and F-actin bundling that can be caused by oxidative stress, mitochondrial dysfunction, or Aβ peptides, all suspected initiators of synaptic loss and neurodegeneration in AD.