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Full-Text Articles in Life Sciences
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 …
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 Cleavage Of The Amyloid Precursor Protein Is Prevented After Overexpression Of Bcl-2 In A Triple Transgenic Mouse Model Of Alzheimer’S Disease, Debra K. Kumasaka, Veronica Galvan, Elizabeth Head, Troy T. Rohn
Caspase Cleavage Of The Amyloid Precursor Protein Is Prevented After Overexpression Of Bcl-2 In A Triple Transgenic Mouse Model Of Alzheimer’S Disease, Debra K. Kumasaka, Veronica Galvan, Elizabeth Head, Troy T. Rohn
Biology Faculty Publications and Presentations
A recent study demonstrated the lack of beta-amyloid (Aβ) plaque formation and accumulation of the amyloid precursor protein (APP) in a triple transgenic mouse model of Alzheimer’s disease (3xTg-AD) following overexpression of the anti-apoptotic protein, Bcl-2 (Rohn et al., J. Neurosci. 28: 3051-9, 2008). The supposition from that study was the accumulation of APP resulted from a decrease in caspase-mediated processing of APP. To determine a direct role for the caspase-cleavage of APP in 3xTg-AD mice, we designed a site-directed caspasecleavage antibody to APP and demonstrated it is a specific marker for caspase-cleaved APP. Application of this antibody revealed neuronal …
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 …