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Full-Text Articles in Life Sciences
Transcriptome Analyses In Bv2 Microglial Cells Following Treatment With Amino-Terminal Fragments Of Apolipoprotein E, Tanner B. Pollock, Giovan N. Cholico, Tarun Suresh, Erica S. Stewart, Madyson M. Mccarthy, Troy T. Rohn
Transcriptome Analyses In Bv2 Microglial Cells Following Treatment With Amino-Terminal Fragments Of Apolipoprotein E, Tanner B. Pollock, Giovan N. Cholico, Tarun Suresh, Erica S. Stewart, Madyson M. Mccarthy, Troy T. Rohn
Biology Faculty Publications and Presentations
Despite the fact that harboring the apolipoprotein E4 (APOE4) allele represents the single greatest risk factor for late-onset Alzheimer’s disease (AD), the exact mechanism by which ApoE4 contributes to disease progression remains unknown. Recently, we demonstrated that a 151 amino-terminal fragment of ApoE4 (nApoE41–151) localizes within the nucleus of microglia in the human AD brain and traffics to the nucleus causing toxicity in BV2 microglia cells. In the present study, we examined in detail what genes may be affected following treatment by nApoE41–151. Transcriptome analyses in BV2 microglial cells following sublethal treatment with nApoE4 …
Proteolytic Cleavage Of Apolipoprotein E In The Down Syndrome Brain, Ryan J. Day, Katie L. Mccarty, Kayla E. Ockerse, Elizabeth Head, Troy T. Rohn
Proteolytic Cleavage Of Apolipoprotein E In The Down Syndrome Brain, Ryan J. Day, Katie L. Mccarty, Kayla E. Ockerse, Elizabeth Head, Troy T. Rohn
Biology Faculty Publications and Presentations
Down syndrome (DS) is one of the most common genetic causes of intellectual disability and is characterized by a number of behavioral as well as cognitive symptoms. Many of the neuropathological features of early-onset Alzheimer’s disease (AD) including senile plaques and neurofibrillary tangles (NFTs) are also present in people with DS as a result of triplication of the amyloid precursor gene on chromosome 21. Evidence suggests that harboring one or both apolipoprotein E4 (APOE4) alleles may increase the risk for AD due to the proteolytic cleavage of apoE4 and a subsequent loss of function. To investigate a role …
Proteolytic Cleavage Of Apolipoprotein E4 As The Keystone For The Heightened Risk Associated With Alzheimer’S Disease, Troy T. Rohn
Proteolytic Cleavage Of Apolipoprotein E4 As The Keystone For The Heightened Risk Associated With Alzheimer’S Disease, Troy T. Rohn
Biology Faculty Publications and Presentations
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by microscopic lesions consisting of beta-amyloid plaques and neurofibrillary tangles (NFTs). The majority of cases are defined as sporadic and are likely caused by a combination of both genetic and environmental factors. Of the genetic risk factors identified, the 34 kDa protein, apolipoprotein (apo) E4, is of significant importance as APOE4 carriers account for 65%–80% of all AD cases. Although apoE4 plays a normal role in lipoprotein transport, how it contributes to AD pathogenesis is currently unknown. One potential mechanism by which apoE4 contributes to disease risk is its propensity to …
Caspase-Cleaved Glial Fibrillary Acidic Protein Within Cerebellar White Matter Of The Alzheimer's Disease Brain, Troy T. Rohn, Lindsey W. Catlin, Wayne W. Poon
Caspase-Cleaved Glial Fibrillary Acidic Protein Within Cerebellar White Matter Of The Alzheimer's Disease Brain, Troy T. Rohn, Lindsey W. Catlin, Wayne W. Poon
Biology Faculty Publications and Presentations
Although the cerebellum is generally thought of as an area spared of Alzheimer's disease (AD) pathology, recent evidence suggests that balance and mobility dysfunction may be magnified in affected individuals. In the present study, we sought to determine the degree of pathological changes within the cerebellum utilizing an antibody that specifically detects caspase-cleaved GFAP within degenerating astrocytes. Compared to control subjects, application of this antibody, termed the GFAP caspase-cleavage product (GFAPccp) antibody, revealed widespread labeling in cerebellar white matter with little staining observed in grey matter. Staining was observed within damaged astrocytes, was often localized near blood vessels and co-localized …
Identification Of An Amino-Terminal Fragment Of Apolipoprotein E4 That Localizes To Neurofibrillary Tangles Of The Alzheimer’S Disease Brain, Troy T. Rohn, Lindsey W. Catlin, Kendra G. Coonse, Jeffrey W. Habig
Identification Of An Amino-Terminal Fragment Of Apolipoprotein E4 That Localizes To Neurofibrillary Tangles Of The Alzheimer’S Disease Brain, Troy T. Rohn, Lindsey W. Catlin, Kendra G. Coonse, Jeffrey W. Habig
Biology Faculty Publications and Presentations
Although the risk factor for harboring the apolipoprotein E4 (apoE4) allele in late-onset Alzheimer’s disease (AD) is well known, the mechanism by which apoE4 contributes to AD pathogenesis has yet to be clarified. Preferential cleavage of the ApoE4 isoform relative to other polymorphic forms appears to be significant, as the resulting fragments are associated with hallmarks of AD. To examine the possible role of apoE4 proteolysis in AD, we designed a site-directed antibody directed at position D172, which would yield a predicted amino-terminal fragment previously identified in AD brain extracts. Western blot analysis utilizing this novel antibody, termed the amino-terminal …
Depletion Of Beclin-1 Due To Proteolytic Cleavage By Caspases In The Alzheimer's Disease Brain, Troy T. Rohn, Ellen Wirawan, Raquel J. Brown, Jordan R. Harris, Eliezer Masliah, Peter Vandenabeele
Depletion Of Beclin-1 Due To Proteolytic Cleavage By Caspases In The Alzheimer's Disease Brain, Troy T. Rohn, Ellen Wirawan, Raquel J. Brown, Jordan R. Harris, Eliezer Masliah, Peter Vandenabeele
Biology Faculty Publications and Presentations
The Beclin-1 protein is essential for the initiation of autophagy and recent studies suggest this function may be compromised in Alzheimer’s disease (AD). In addition, in vitro studies have supported a loss of function of Beclin-1 due to proteolytic modification by caspases. In the present study we examined whether caspase-cleavage of Beclin-1 occurs in the AD brain by designing a site-directed caspase-cleavage antibody based upon a known cleavage site within the protein at position D149. We confirmed that Beclin-1 is an excellent substrate for caspase-3 and demonstrate cleavage led to the formation of a 35 kDa C-terminal fragment labeled by …
Caspase-Cleaved Tar Dna Binding Protein-43 Is A Major Pathological Finding In Alzheimer’S Disease, Troy T. Rohn
Caspase-Cleaved Tar Dna Binding Protein-43 Is A Major Pathological Finding In Alzheimer’S Disease, Troy T. Rohn
Biology Faculty Publications and Presentations
The TAR DNA binding protein-43 (TDP-43) has been identified as a major constituent of inclusions found in frontotemporal dementia with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). To determine a possible role for TDP-43 in Alzheimer’s disease (AD), a site-directed caspase-cleavage antibody to TDP-43 based upon a known caspase-3 cleavage consensus site within TDP-43 at position D219 was designed. In vitro, this antibody labeled the predicted 25 kDa caspase-cleavage fragment of TDP-43 without labeling full-length TDP-43 following digestion of recombinant TDP-43 with caspase-3 or treatment of Hela cells with staurosporine. Application of this antibody in postmortem brain sections …