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P3–213: Regulation of apoptotic cell death by two members of the presenilin–dependent G–secretase complex : APH–1 and PEN–2
Author(s) -
Dunys Julie,
Kawarai Toshitaka,
St. George-Hyslop Peter,
Alves da Costa Cristine,
Checler Frédéric
Publication year - 2006
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.2006.05.1482
Subject(s) - presenilin , nicastrin , programmed cell death , biology , microbiology and biotechnology , propidium iodide , apoptosis , transactivation , alzheimer's disease , transcription factor , biochemistry , pathology , medicine , disease , gene
Background: Apoptosis-related cellular signalling molecules, including death receptors and caspases, have been implicated in AD, though their role in AD neuropathology remains unclear. The death receptors TNF-R1 and Fas can initiate cell death through recruitment of pro-caspases to the cytoplasmic adaptor protein FADD and, in addition, the pro-survival protein cFLIP, a caspase homolog, can be recruited to this complex. We have previously shown that cFLIP is present in human and murine cerebral cortex, and that abundance increases following traumatic injury (Hainsworth et al 2005). We plan to analyse the interactions of cFLIP, FADD and other apoptosis-related proteins in human brain, as a clue to their possible effects. Objectives: Here, our aim was to examine the abundance of apoptosis-related proteins in control and AD frontal cortex, an area where neuropathological signs appear relatively late in AD progression. Methods: Frozen post mortem tissue was obtained from the MRC London Neurodegenerative Diseases Brain Bank, Institute of Psychiatry. Frontal cortical tissue was from patients with medium-severe AD (median age 91, range 71-93, n 6). Control frontal cortical samples were from patients whose cause of death was non-CNS illness related (median age 79, range 61-95, n 6). Proteins were detected by Western blot analysis and relative abundance estimated by semi-quantitative densitometry. Results: FADD and the short form of cFLIP (delta isoform, MW 28 kDa) were detected in all samples. The abundance of the cFLIPprotein, relative to the cellular housekeeping protein -actin, was greater in the AD group than in the control group (p 0.05, Mann-Whitney U-test) while the abundance of FADD was not significantly different. Conclusions: FADD and cFLIPproteins are present in non-dementia and AD frontal cortex. This will allow protein interactions to be tested.