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P2‐002: A description of adult child and spouse caregivers of persons with Alzheimer's disease: Reactions to loss
Author(s) -
Steinwedel Cynthia M.,
Ott Carol H.,
Morgan Sarah
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.1022
Subject(s) - spouse , grief , thematic analysis , psychology , dementia , clinical psychology , family caregivers , caregiver burden , coping (psychology) , developmental psychology , psychiatry , qualitative research , disease , gerontology , medicine , social science , sociology , anthropology , pathology
FTLD-TAU, hyperphosphorylated forms of tau are the major constituent of lesions, while in FTLD-TDP the TAR-DNA-binding Protein 43 (TDP-43) deposits, and in FTLD-FUS it is the protein fused in sarcoma (FUS, also known as translocated in liposarcoma (TLS) or heterogenous ribonuclear protein (hnRNP)) that forms inclusions. Similarly, FUS deposits are found in amyotrophic lateral sclerosis (ALS), the most common form of motor neuron degeneration. A pathogenic role of FUS in neurodegeneration is further supported by the identification of mutations in FUS in ALS. As a transcription factor, FUS is mainly localized to the nucleus, where it interacts with other transcription factors and regulates RNA-expression. Furthermore, FUS contributes to the regulation of actin cytoskeleton in the cytoplasm. Methods: Here we use lentiviral MISSIONTM siRNA driven knock-down to study the effects of FUS reduction in SH-SY5Y neuroblastoma and HeLa cervical cancer cells. Cells were analyzed by fluorescenceactivated-cell-sorting (FACS), Western blotting and immunocytochemistry (ICC). Results: Levels of knock-down of FUS were determined by Western Blots, FACS and ICC. FUS levels were reduced by 30 to 90% in different stably selected lines. Reduction of FUS resulted in increased numbers of apoptotic cell death as determined by Annexin-V and Sytox labeling. In addition, FUS reduction is associated with increased amount of cleaved caspase 3. Conclusions: Loss of FUS is associated with an increase in apoptotic cell death in both SH-SY5Y and HeLa-cells. Hence in disease, loss-of-physiological-function of FUS associated with its aggregation in the cytoplasm may contribute to neurodegeneration in FTLD and ALS.