title: Neuroserpin up-regulation in the Alzheimer's disease brain is associated with elevated thyroid hormone receptor-β1 and HuD expression.
abstract: Neuroserpin, the major inhibitor of tissue plasminogen activator (tPA) in brain, has been shown to be up-regulated in Alzheimer's disease (AD). Inhibition of tPA activity leads to reduced brain levels of plasmin, one of the main enzymes responsible for the degradation and clearance of amyloid-beta and its plaques from the brain. Thyroid hormone is one of the few factors known to enhance expression of neuroserpin in neurons. Thyroid hormone acts on neurons by binding to its receptors THR1α and THR1β, which then function in the nucleus to up-regulate the expression of numerous genes including the RNA-binding protein HuD. HuD acts post-transcriptionally to enhance expression of numerous proteins including neuroserpin by stabilizing their mRNAs. A series of Alzheimer's disease brain tissues were compared to age-matched control brains for their expression of neuroserpin, THRβ1 and HuD by western blotting. Alzheimer's disease brain tissues with elevated neuroserpin protein also showed increased expression of THRβ1 and HuD. Pair-wise analyses showed significant correlation p-values between neuroserpin, THRβ1 and HuD levels; suggesting that the up-regulation of neuroserpin in Alzheimer's disease brain may result from an activation of the thyroid hormone response system in these individuals. These findings provide evidence for a potential relationship between thyroid hormone disorders and Alzheimer's disease.
authors.affiliation: Cell Biology & Physiology, University of New Mexico HSC, Albuquerque, NM, USA.
authors.forename: Bobban
authors.initials: B
authors.lastname: Subhadra
authors.forename: Kristin
authors.initials: K
authors.lastname: Schaller
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Seeds
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D051959:ELAV Proteins / Q000378:metabolism*; D000067779:ELAV-Like Protein 4; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D015843:Serpins / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism*; D015854:Up-Regulation; D000097522:Neuroserpin
chemical_list: D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; D009479:Neuropeptides; D015843:Serpins; D037042:Thyroid Hormone Receptors beta; D000097522:Neuroserpin; C498010:ELAVL4 protein, human
keywords: AD; APP; Alzheimer’s disease; Aβ; Hu protein D; HuD; Human disease brain; Hyperthyroidism; NS; Neuroserpin; THRβ1; Thyroid hormone receptor-β1; Tissue plasminogen activator; amyloid precursor protein; amyloid-beta protein; neuroserpin; thyroid hormone receptor-beta 1
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