Aging and Alzheimer’s disease connection: Nuclear Tau and lamin A

Gil, Laura; Niño, Sandra A.; Capdeville, Gabriela; Jiménez‐Capdeville, María E.

doi:10.1016/j.neulet.2021.135741

Cited by 17 publications

(19 citation statements)

References 162 publications

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“…As recently shown, hippocampal neurogenesis and plasticity of the entire hippocampal circuitry are linked to the DG and are found to sharply drop in AD ( 21 ). Further, we deliberately do not focus on plaques and tangles in AD, which have already been targeted by a high number of studies, but address in particular the nuclear structure of the DG neurons, since recent evidence points to a nuclear origin of AD ( 22 ) including chromatin structures ( 23 ). In addition, we also include 3D imaging examples of other parts and structures of the hippocampus and provide the corresponding statistical analysis.…”

mentioning

confidence: 99%

Three-dimensional virtual histology of the human hippocampus based on phase-contrast computed tomography

Eckermann

Schmitzer

Meer

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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We have studied the three-dimensional (3D) cytoarchitecture of the human hippocampus in neuropathologically healthy and Alzheimer’s disease (AD) individuals, based on phase-contrast X-ray computed tomography of postmortem human tissue punch biopsies. In view of recent findings suggesting a nuclear origin of AD, we target in particular the nuclear structure of the dentate gyrus (DG) granule cells. Tissue samples of 20 individuals were scanned and evaluated using a highly automated approach of measurement and analysis, combining multiscale recordings, optimized phase retrieval, segmentation by machine learning, representation of structural properties in a feature space, and classification based on the theory of optimal transport. Accordingly, we find that the prototypical transformation between a structure representing healthy granule cells and the pathological state involves a decrease in the volume of granule cell nuclei, as well as an increase in the electron density and its spatial heterogeneity. The latter can be explained by a higher ratio of heterochromatin to euchromatin. Similarly, many other structural properties can be derived from the data, reflecting both the natural polydispersity of the hippocampal cytoarchitecture between different individuals in the physiological context and the structural effects associated with AD pathology.

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mentioning

confidence: 99%

Three-dimensional virtual histology of the human hippocampus based on phase-contrast computed tomography

Eckermann

Schmitzer

Meer

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…63 Experimental approaches such as neuroproteomics, 25 laser capture microdissection coupled with mass spectrometry, 64,65 and interactome studies have been instrumental for the interrogation of Tau interactions with other molecules, 63,66,67 and in organoid 68 and mouse models. 69 Tau was found to interact with deoxyribonucleic acid (DNA) 70 and ribonucleic acid (RNA), 71 strongly suggesting that it has important regulatory roles in the nucleus, 2,72 such as wide-scale chromatin reorganization, detected in AD brain, 73 as well as through posttranscriptional regulation of multiple gene transcripts (Fig. 1C, RNA transcripts).…”

Section: Cellular Processesmentioning

confidence: 99%

Revisiting the grammar of Tau aggregation and pathology formation: how new insights from brain pathology are shaping how we study and target Tauopathies

Limorenko

Lashuel

2022

Chem. Soc. Rev.

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“…There is increasing evidence that tau and α-synucleinproteins that are elevated in both AD and PDplay an important role in DDR in neurodegenerative disease. − DNA-repair mechanisms include direct lesion repair (e.g., MGMT for O 6 -mG lesions), selective excision of bases (e.g., OGG1 for 8-oxoG lesions) and of nucleosides (e.g., UV damage), , with refusion of the corrected single DNA strands, and double-strand break repair by homologous recombination and nonhomologous end-joining (NHEJ) . Whereas postmitotic cells and cycling cells in G 1 phase of the cell cycle use NHEJ to seal double-strand breaks, HR occurs only during S- and G 2 phases of cycling cells because the mechanism requires a sister chromatid.…”

Section: Molecular Actions Of Hydrazine-related Compoundsmentioning

confidence: 99%

Role of Hydrazine-Related Chemicals in Cancer and Neurodegenerative Disease

Spencer

Kisby

2021

Chem. Res. Toxicol.

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Hydrazine-related chemicals (HRCs) with carcinogenic and neurotoxic potential are found in certain mushrooms and plants used for food and in products employed in various industries, including aerospace. Their propensity to induce DNA damage (mostly O 6-, N7- and 8-oxo-guanine lesions) resulting in multiple downstream effects is linked with both cancer and neurological disease. For cycling cells, unrepaired DNA damage leads to mutation and uncontrolled mitosis. By contrast, postmitotic neurons attempt to re-enter the cell cycle but undergo apoptosis or nonapoptotic cell death. Biomarkers of exposure to HRCs can be used to explore whether these substances are risk factors for sporadic amyotrophic laterals sclerosis and other noninherited neurodegenerative diseases, which is the focus of this paper.

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Aging and Alzheimer’s disease connection: Nuclear Tau and lamin A

Cited by 17 publications

References 162 publications

Three-dimensional virtual histology of the human hippocampus based on phase-contrast computed tomography

Three-dimensional virtual histology of the human hippocampus based on phase-contrast computed tomography

Revisiting the grammar of Tau aggregation and pathology formation: how new insights from brain pathology are shaping how we study and target Tauopathies

Role of Hydrazine-Related Chemicals in Cancer and Neurodegenerative Disease

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