scholarly journals Therapeutic targeting of nuclear receptors, liver X and retinoid X receptors, for Alzheimer's disease

2019 ◽  
Vol 176 (18) ◽  
pp. 3599-3610 ◽  
Author(s):  
Nicholas F. Fitz ◽  
Kyong Nyon Nam ◽  
Radosveta Koldamova ◽  
Iliya Lefterov
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nuclear Receptors ◽  
Therapeutic Targeting ◽  
Retinoid X Receptors ◽  
X Receptors

P2-255: Optimizing the therapeutic targeting of alpha7 nAChR for the treatment of Alzheimer's disease

2009 ◽  
Vol 5 (4S_Part_11) ◽  
pp. P335-P335
Author(s):  
Roger L. Papke ◽  
Gretchen Y. López-Hernández ◽  
Nicole A. Horenstein
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Targeting

scholarly journals Widely spaced, directly repeated PuGGTCA elements act as promiscuous enhancers for different classes of nuclear receptors.

1995 ◽  
Vol 15 (11) ◽  
pp. 5858-5867 ◽  
Author(s):  
S Kato ◽  
H Sasaki ◽  
M Suzawa ◽  
S Masushige ◽  
L Tora ◽  
...  
Keyword(s):  
Vitamin D ◽  
Nuclear Receptors ◽  
Response Element ◽  
Binding Motifs ◽  
Retinoid X Receptors ◽  
Response Elements ◽  
Cis Acting ◽  
X Receptors ◽  
Receptor Cross Talk ◽  
Site Recognition

We describe here a novel class of cis-acting response elements for retinoid, vitamin D, and estrogen receptors which are widely spaced (10 to 200 bp) direct repeats (DRs) of the canonical 5'-AGGTCA half-site recognition motif (DR10 to DR200). In contrast to the specificity previously observed with shortly spaced DRs (DR1 to DR5), the different receptors bind promiscuously to these novel elements to activate transcription in the presence of retinoic acid (RA), vitamin D, or estrogen. The greatest RA-dependent transactivation, seen with DR15, was similar to that observed with the canonical DR5. Both RA receptors and retinoid X receptors contribute to transactivation through widely spaced DR elements. With the estrogen receptor, DR15 was one-third as efficient as the classical palindromic response element. A further increase of spacer lengths progressively decreased the efficiency of transactivation. No transactivation was seen with widely spaced DRs when the thyroid and retinoid X receptors were coexpressed in the presence of their ligands. The progesterone receptor was also unable to transactivate through a DR10 element composed of its cognate binding motifs. These results considerably extend the response element repertoire of nuclear receptors and suggest the existence of promiscuous transcriptional regulation through common response elements, as well as the possibility of receptor "cross-talk."

THERAPEUTIC TARGETING OF TREM2 BY AN ACTIVATING ANTIBODY AMELIORATES AMYLOID-BETA DEPOSITION AND IMPROVES COGNITION IN THE 5XFAD MODEL OF ALZHEIMER’S DISEASE

2019 ◽  
Vol 15 (7) ◽  
pp. P214
Author(s):  
Brittani R. Price ◽  
Tiffany L. Sudduth ◽  
Erica M. Weekman ◽  
Abigail Woolums ◽  
Danielle Hawthorne ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Therapeutic Targeting ◽  
Model Of Alzheimer’S Disease

scholarly journals Impact of HMGB1, RAGE, and TLR4 in Alzheimer’s Disease (AD): From Risk Factors to Therapeutic Targeting

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 383 ◽  
Author(s):  
Yam Nath Paudel ◽  
Efthalia Angelopoulou ◽  
Christina Piperi ◽  
Iekhsan Othman ◽  
Khurram Aamir ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
High Mobility ◽  
Health Concern ◽  
Hmgb1 Protein ◽  
Therapeutic Targeting ◽  
Beneficial Effects ◽  
Molecular Pattern ◽  
Glycation End Products

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder and a leading cause of dementia, with accumulation of amyloid-beta (Aβ) and neurofibrillary tangles (NFTs) as defining pathological features. AD presents a serious global health concern with no cure to date, reflecting the complexity of its pathogenesis. Recent evidence indicates that neuroinflammation serves as the link between amyloid deposition, Tau pathology, and neurodegeneration. The high mobility group box 1 (HMGB1) protein, an initiator and activator of neuroinflammatory responses, has been involved in the pathogenesis of neurodegenerative diseases, including AD. HMGB1 is a typical damage-associated molecular pattern (DAMP) protein that exerts its biological activity mainly through binding to the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4). RAGE and TLR4 are key components of the innate immune system that both bind to HMGB1. Targeting of HMGB1, RAGE, and TLR4 in experimental AD models has demonstrated beneficial effects in halting AD progression by suppressing neuroinflammation, reducing Aβ load and production, improving spatial learning, and inhibiting microglial stimulation. Herein, we discuss the contribution of HMGB1 and its receptor signaling in neuroinflammation and AD pathogenesis, providing evidence of its beneficial effects upon therapeutic targeting.

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