Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Frontotemporal dementia (FTD) is a neurodegenerative disease associated with aging for which the etiology is unclear. Relatively little is known about the pathology of this disease, which has only recently been a topic of investigation for dementia researchers. Though the known pathology of FTD includes neuron loss, the mechanism of neuronal death is not known. In this study, the authors investigated apoptotic pathways as a possible mechanism of neuronal cell death in FTD. They evaluated immunoreactivity for Bcl-2 family protein members Bcl-x and Bax in postmortem frontal cortex from FTD, AD, and control cases. Bcl-x(L), Bcl-x(S), and Bax all exhibited altered immunoreactivity in FTD cases as compared with control cases. Bcl-x immunoreactivity varied widely among both controls and FTD cases. However, Bcl-x(L) showed strong white matter immunoreactivity in all FTD cases, whereas white matter immunoreactivity was absent in controls. These trends in Bcl-x immunoreactivity suggest a strong white matter involvement in the pathology of FTD. Bax immunoreactivity also varied across all cases. Bax immunoreactivity was observed in terminal transferase dUTP nick ending labeling (TUNEL) positive neurons in both FTD and AD cases. However, one notable finding was immunoreactivity to Bax in astrocytes of FTD cases, as well as endothelial cells of the cerebrovasculature. Neither astrocytic nor endothelial cell immunoreactivity to Bax was exhibited in control or AD cases. Because Bax is a pro-apoptotic protein, this finding suggests the presence of a cerebrovascular component in the pathology of FTD. These findings, coupled with the proposed functions of the Bcl-2 family proteins, suggest that an apoptotic pathway may be responsible for neuron, and possibly astrocyte, death in FTD.
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PMID:Bcl-2 family protein behavior in frontotemporal dementia implies vascular involvement. 1140 49

Frontotemporal dementia (FTD) is caused by the progressive degeneration of the frontal and temporal lobes of the brain. Behavioral variant FTD (bvFTD) is the most common clinical subtype of FTD and pathological subtypes of bvFTD are known as FTD-tau, transactive response (TAR) DNA-binding protein 43 (TDP-43), and fused in sarcoma (FUS). Pathological mechanisms of bvFTD are largely unknown. In this study, we investigated the expression of pathological markers, such as p-Tau, TDP-43, and FUS, in the induced pluripotent stem-cell-derived neurons (iPSN) from two sporadic bvFTD patients and one normal subject. We also used an FTD-patient-derived iPSC-line-carrying microtubule-associated protein tau (MAPT) P301L point mutation as positive control for p-Tau expression. Staurosporine (STS) was used to induce cellular stress in order to investigate dynamic cellular responses related to the cell death pathway. As a result, the expression of active caspase-3 was highly increased in the bvFTD-iPSNs compared with control iPSNs in the STS-treated conditions. Other cell-death-related proteins, including Bcl-2-associated X protein (Bax)/Bcl-2 and cytochrome C, were also increased in the bvFTD-iPSNs. Moreover, we observed abnormal expression patterns of TDP-43 and FUS in the bvFTD-iPSNs compared with control iPSNs. We suggest that the iPSC technology might serve as a potential tool to demonstrate neurodegenerative phenotypes of bvFTD, which will be useful for studying pathological mechanisms for FTD as well as related drug screening in the future.
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PMID:Modeling of Frontotemporal Dementia Using iPSC Technology. 3272 73