BRCA1 and p53 Tumor Suppressor Molecules in Alzheimer’s Disease

Abnormal differentiation and growth of hematopoietic stem cells cause the development of hematopoietic diseases and hematopoietic malignancies. However, the molecular events underlying leukemia development are not well understood. In our recent study, we have demonstrated that calcium ionophore and phorbol ester force the differentiation of T lymphoblastic leukemia. The event involves a newly identified IκBα/WWOX/ERK signaling, in which WWOX is Ser14 phosphorylated. Additional evidence also reveals that pS14-WWOX is involved in enhancing cancer progression and metastasis and facilitating neurodegeneration. In this mini-review, we update the current knowledge for the functional roles of WWOX under physiological and pathological settings, and provide new insights regarding pS14-WWOX in T leukemia cell maturation, and switching the anticancer pY33-WWOX to pS14-WWOX for cancer promotion and disease progression. Impact statement WWOX was originally designated as a tumor suppressor. However, human newborns deficient in WWOX do not spontaneously develop tumors. Activated WWOX with Tyr33 phosphorylation is present in normal tissues and organs. However, when pY33-WWOX is overly induced under stress conditions, it becomes apoptotic to eliminate damaged cells. Notably, WWOX with Ser14 phosphorylation is upregulated in the lesions of cancer, as well as in the brain hippocampus and cortex with Alzheimer’s disease. Suppression of pS14-WWOX by Zfra reduces cancer growth and mitigates Alzheimer’s disease progression, suggesting that pS14-WWOX facilitates disease progression. pS14-WWOX can be regarded as a marker of disease progression.

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Cognitive control constrains memory attributions

Behavioral and Brain Sciences ◽

10.1017/s0140525x19001869 ◽

2019 ◽

Vol 42 ◽

Author(s):

Colleen M. Kelley ◽

Larry L. Jacoby

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Cognitive Control

Abstract Cognitive control constrains retrieval processing and so restricts what comes to mind as input to the attribution system. We review evidence that older adults, patients with Alzheimer's disease, and people with traumatic brain injury exert less cognitive control during retrieval, and so are susceptible to memory misattributions in the form of dramatic levels of false remembering.

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Review for "Expression profiling of precuneus layer III cathepsin D‐immunopositive pyramidal neurons in mild cognitive impairment and Alzheimer's disease: Evidence for neuronal signaling vulnerability"

10.1002/cne.24929/v2/review1 ◽

2020 ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Expression Profiling ◽

Cathepsin D ◽

Pyramidal Neurons ◽

Neuronal Signaling

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Formation of paired helical filaments in Alzheimer's disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100111628 ◽

1984 ◽

Vol 42 ◽

pp. 302-303

Author(s):

J. Metuzals ◽

D. F. Clapin ◽

V. Montpetit

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Frontal Lobe ◽

Giant Axon ◽

Paired Helical Filaments ◽

Normal Brain ◽

Protein Assemblies ◽

Electron Microscopic ◽

Helical Symmetry ◽

Structural Levels

Information on the conformation of paired helical filaments (PHF) and the neurofilamentous (NF) network is essential for an understanding of the mechanisms involved in the formation of the primary lesions of Alzheimer's disease (AD): tangles and plaques. The structural and chemical relationships between the NF and the PHF have to be clarified in order to discover the etiological factors of this disease. We are investigating by stereo electron microscopic and biochemical techniques frontal lobe biopsies from patients with AD and squid giant axon preparations. The helical nature of the lesion in AD is related to pathological alterations of basic properties of the nervous system due to the helical symmetry that exists at all hierarchic structural levels in the normal brain. Because of this helical symmetry of NF protein assemblies and PHF, the employment of structure reconstruction techniques to determine the conformation, particularly the handedness of these structures, is most promising. Figs. 1-3 are frontal lobe biopsies.

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Computer-aided methods for 3-D visualization of serial sections and thick biological specimens

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100129930 ◽

1992 ◽

Vol 50 (2) ◽

pp. 1060-1061

Author(s):

Mark Ellisman ◽

Maryann Martone ◽

Gabriel Soto ◽

Eleizer Masliah ◽

David Hessler ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Three Dimensional ◽

Neuritic Plaque ◽

Dimensional Structure ◽

Data Sets ◽

Molecular Physiology ◽

Research Activities ◽

Computer Aided ◽

Dimensional Reconstruction

Structurally-oriented biologists examine cells, tissues, organelles and macromolecules in order to gain insight into cellular and molecular physiology by relating structure to function. The understanding of these structures can be greatly enhanced by the use of techniques for the visualization and quantitative analysis of three-dimensional structure. Three projects from current research activities will be presented in order to illustrate both the present capabilities of computer aided techniques as well as their limitations and future possibilities.The first project concerns the three-dimensional reconstruction of the neuritic plaques found in the brains of patients with Alzheimer's disease. We have developed a software package “Synu” for investigation of 3D data sets which has been used in conjunction with laser confocal light microscopy to study the structure of the neuritic plaque. Tissue sections of autopsy samples from patients with Alzheimer's disease were double-labeled for tau, a cytoskeletal marker for abnormal neurites, and synaptophysin, a marker of presynaptic terminals.

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Liquid crystalline ordering of paired helical filaments in neurofibrillary tangles of Alzheimer's disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100143365 ◽

1986 ◽

Vol 44 ◽

pp. 348-349

Author(s):

D.F. Clapin ◽

V.J.A. Montpetit

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurofibrillary Tangles ◽

Liquid Crystalline ◽

Amyloid Fibrils ◽

Geometric Analysis ◽

Paired Helical Filaments ◽

Microscopic Level ◽

Light Microscopic Level ◽

Regular Spacing

Alzheimer's disease is characterized by the accumulation of abnormal filamentous proteins. The most important of these are amyloid fibrils and paired helical filaments (PHF). PHF are located intraneuronally forming bundles called neurofibrillary tangles. The designation of these structures as "tangles" is appropriate at the light microscopic level. However, localized domains within individual tangles appear to demonstrate a regular spacing which may indicate a liquid crystalline phase. The purpose of this paper is to present a statistical geometric analysis of PHF packing.

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Paired helical filaments (PHF) in rats: An experimental animal model for Alzheimer's disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100128493 ◽

1987 ◽

Vol 45 ◽

pp. 842-843

Author(s):

V.J.A. Montpetit ◽

S. Dancea ◽

S.W. French ◽

D.F. Clapin

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Animal Model ◽

Paired Helical Filaments ◽

Ethanol Intoxication ◽

Drg Neurons ◽

Critical Difference ◽

Suitable Animal Model ◽

The Central Nervous System ◽

Chronic Ethanol Intoxication

A continuing problem in Alzheimer research is the lack of a suitable animal model for the disease. The absence of neurofibrillary tangles of paired helical filaments is the most critical difference in the processes by which the central nervous system ages in most species other than man. However, restricting consideration to single phenomena, one may identify animal models for specific aspects of Alzheimer's disease. Abnormal fibers resembling PHF have been observed in dorsal root ganglia (DRG) neurons of rats in a study of chronic ethanol intoxication and spontaneously in aged rats. We present in this report evidence that PHF-like filaments occur in ethanol-treated rats of young age. In control animals lesions similar in some respects to our observations of cytoskeletal pathology in pyridoxine induced neurotoxicity were observed.Male Wistar BR rats (Charles River Labs) weighing 350 to 400 g, were implanted with a single gastrostomy cannula and infused with a liquid diet containing 30% of total calories as fat plus ethanol or isocaloric dextrose.

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