Neuron-specific localisation of the TR3 death receptor in Alzheimer's disease.
Death receptors are associated with the homeostatic and pathologic induction of cell death. TR3 is a recently characterised member of the death receptor family that is expressed in the adult brain. In order to establish the role of TR3 in acute CNS disease and chronic neurodegeneration, we analysed brain regions from Alzheimer's disease (AD), stroke and neurotrauma patients, using a novel anti-peptide antibody generated to an exposed epitope in the extracellular domain of the receptor. We show a statistically significant increase in TR3 protein levels in AD brain samples but not in stroke, neurotrauma or control samples. The increase observed for TR3 was specific to neurons in regions associated with AD pathology. This is the first report describing the neuron-specific regulation of a death receptor in chronic disease and may indicate that a TR3 receptor-mediated signalling pathway is involved in AD-associated neuronal loss.
Newman
S J
SJ
Department of Analytical Science, SmithKline Beecham Pharmaceuticals, Third Avenue, Harlow, Essex CM19 5AW, UK.
Bond
B
B
Crook
B
B
Darker
J
J
Edge
C
C
Maycox
P R
PR
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology*; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D006259:Craniocerebral Trauma / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000473:pathology* / Q000502:physiology*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D020521:Stroke / Q000503:physiopathology; D014157:Transcription Factors / Q000032:analysis*
D004268:DNA-Binding Proteins; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors