Life Sciences Commons^™

Importin-Mediated Pathological Tau Nuclear Translocation Causes Disruption Of The Nuclear Lamina, Tdp-43 Mislocalization And Cell Death, Robert F. Candia, Leah S. Cohen, Viktoriya Morozova, Christopher Corbo, Alejandra D. Alonso

Publications and Research

Tau is a cytosolic protein that has also been observed in the nucleus, where it has multiple proposed functions that are regulated by phosphorylation. However, the mechanism underlying the nuclear import of tau is unclear, as is the contribution of nuclear tau to the pathology of tauopathies. We have previously generated a pathological form of tau, PH-tau (pseudophosphorylation mutants S199E, T212E, T231E, and S262E) that mimics AD pathological behavior in cells, Drosophila, and a mouse model. Here, we demonstrated that PH-tau translocates into the nucleus of transiently transfected HEK-293 cells, but wildtype tau does not. We identified a putative …

Effect Of Cntf Derived Peptide, P021 On Cognition And Pathology In 3xtg-Ad Mouse Model Of Alzheimer's Disease, Narjes Baazaoui

Dissertations, Theses, and Capstone Projects

Studies described in this thesis deal with the preventive effects of a neurogenic/neurotropic peptidergic compound, P021, on neurogenesis and synaptic deficits, neurodegeneration, cognitive impairment, and Ab and tau pathologies in a 3xTg-AD mouse model of Alzheimer’s disease (AD).

Background: AD is a chronic progressive neurodegenerative disease. Its multifactorial nature and the heterogeneity make its treatment especially challenging. Although it is a major burden in society, at present there is no drug that can stop or slow down the progression of the disease. Currently, the only available treatments are symptomatic and for mild to severe stages. The development of a drug …

Screen For Suppressors And Enhancers Of Excitotoxic Neurodegeneration, Anthony Omorodion Edokpolo

Dissertations and Theses

Excitotoxicity is an important and frequently observed neurodegenerative process. Excitotoxicity mediates brain damage in a range of diseases and conditions including stroke, and is triggered by excessive stimulation of glutamatergic synapses. In spite of extensive studies, the molecular mechanisms involved in excitotoxicity following the over-activation of postsynaptic glutamate receptors are not well understood, and clinical trials based on our partial understanding of the process ended with disappointment. Genetic screens in simple animal models offer a powerful alternative approach, since screens are unbiased, analysis is facilitated by strong research tools, and cellular mechanisms are highly conserved through evolution. We produced a …

Glia-Mediated Neurodegeneration In The Drosophila Melanogaster Cns, Ivan J. Santiago

Dissertations and Theses

No abstract provided.

Morphological And Neuroanatomical Changes Associated With The Induction Of Neurodegeneration And Life Span Reduction In Drosophila Melanogaster By Glia Targeted Expression Of Cdh1/Rap/Fzr, An Activator Of The Anaphase Promoting Complex, Israel Nnah

Dissertations and Theses

"The retina aberrant in pattern (rap) gene encodes the Fizzy-related protein (Fzr), an activator of the E3 ubiquitin ligase complex: the Anaphase Promoting Complex/Cyclosome (APC/C). APC/C facilitates the cell cycle stage-specific degradation of cyclins and other mitotic regulators, resulting in the inactivation of Cdk (Cyclin Dependent Kinase) complexes, thus promoting completion of mitosis. Previous studies from our laboratory have shown that Rap/Fzr (the Drosophila homolog of the mammalian Cdh1) regulates glia differentiation and promotes neuron formation. Recent studies have shown that the glia specific over expression of Rap/Fzr causes progressive neurodegeneration and life span reduction preceded by temperature sensitive paralysis, …