Development of Positron-Emission Tomography/Single-Photon Emission Computed Tomography Imaging Probes for in Vivo Detection of .BETA.-Amyloid Plaques in Alzheimer's Brains

Ono, Masahiro

doi:10.1248/cpb.57.1029

Cited by 38 publications

(23 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation suggests that a critical turning point exists in the onset of AD after increased generation of Aβ. As discussed in this Forum issue, many novel factors, such as TEK/Tie2 (48) (52). In conclusion, not only is the understanding of pathogenic mechanisms by which such novel molecules mediate disease onset and progression important but also the development of diagnostics using novel probes is essential for the establishment of treatments utilizing new drugs for neurodegenerative diseases including AD.…”

Section: Discussionmentioning

confidence: 99%

Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of Alzheimer’s Disease: Possible Involvement of HRD1, a Novel Molecule Related to Endoplasmic Reticulum Stress, in Alzheimer’s Disease

2012

View full text Add to dashboard Cite

Abstract. Endoplasmic reticulum (ER)-associated degradation (ERAD) is a protective mechanism against ER stress in which unfolded proteins accumulated in the ER are selectively transported to the cytosol for degradation by the ubiquitin-proteasome system. We cloned the novel ubiquitin ligase HRD1, which is involved in ERAD, and showed that HRD1 promoted amyloid precursor protein (APP) ubiquitination and degradation, resulting in decreased generation of amyloid β (Aβ). In addition, suppression of HRD1 expression caused APP accumulation and promoted Aβ generation associated with ER stress and apoptosis. Interestingly, HRD1 levels were significantly decreased in the cerebral cortex of patients with Alzheimer's disease (AD), and the brains of these patients experienced ER stress. Our recent study revealed that this decrease in HRD1 was due to its insolubilization; however, controversy persists about whether the decrease in HRD1 protein promotes Aβ generation or whether Aβ neurotoxicity causes the decrease in HRD1 protein levels. Here, we review current findings on the mechanism of HRD1 protein loss in the AD brain and the involvement of HRD1 in the pathogenesis of AD. Furthermore, we propose that HRD1 may be a target for novel AD therapeutics.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of Alzheimer’s Disease: Possible Involvement of HRD1, a Novel Molecule Related to Endoplasmic Reticulum Stress, in Alzheimer’s Disease

2012

View full text Add to dashboard Cite

show abstract

“…5-(3-(Tributylstannyl)phenyl)furan-2-carbaldehyde (9). A mixture of 8 (50 mg, 0.2 mmol), bis(tributyltin) (0.4 mL), and (Ph 3 P) 4 Pd (50 mg, 0.04 mmol) in a mixed solvent (9 mL, 5:4 dioxane/triethylamine mixture) was stirred for 3 h under reflux. The solvent was removed, and the residue was purified by silica gel chromatography (hexane/ethyl acetate = 9/1) to give 37 mg of 9 (40.0%).…”

Section: Z)-ethyl 2-(5-((5-(3-iodophenyl)furan-2-yl)methylene)-4-oxo-mentioning

confidence: 99%

“…5-(3-Iodophenyl)furan-2-carbaldehyde (1). To a solution of 5-formyl-2-furanboronic acid (280 mg, 2 mmol) and 1,3-diiodobenzene (660 mg, 2 mmol) in dimethoxyethane (15 mL) were added (Ph 3 P) 4 Pd (114 mg, 0.1 mmol) and 2 M Na 2 CO 3 (4.6 mL). The reaction mixture was stirred for 3 h under reflux.…”

mentioning

confidence: 99%

Rhodanine and Thiohydantoin Derivatives for Detecting Tau Pathology in Alzheimer’s Brains

Ono

Hayashi²,

Matsumura³

et al. 2011

ACS Chem. Neurosci.

Self Cite

View full text Add to dashboard Cite

A novel series of rhodanin (RH) and thiohydantoin (TH) derivatives were designed and synthesized for detecting tau pathology in the brains of patients with Alzheimer’s disease (AD). In experiments in vitro using tau and β-amyloid (Aβ) aggregates, the TH derivative, TH2, showed high specific binding to tau aggregates. In hippocampal sections obtained from AD patients, TH2 intensely stained neurofibrillary tangles. In experiments using normal mice, [125I]TH2 showed good uptake (1.54%ID/g, 2 min postinjection) into and a rapid washout (0.25%ID/g, 60 min postinjection) from the brain. [123I]TH2 should be further investigated as a potential imaging agent for detecting tau pathology.

show abstract

“…9 The development of PET imaging probes for in vivo detection of Alzheimer"s brains is critical for early and accurate diagnosis and for the successful discovery of disease-modifying therapies. [10][11][12] Aggregated -amyloid plaques (A) and tau protein are two major biomarkers for AD. 13 16 as displayed in Figure 1.…”

mentioning

confidence: 99%

Synthesis of a PET tau tracer [11C]PBB3 for imaging of Alzheimer’s disease

Wang

Gao

et al. 2015

Bioorganic & Medicinal Chemistry Letters

View full text Add to dashboard Cite

Abstract-The authentic standard PBB3 and its precursor N-desmethyl-PBB3 as well as TBS-protected N-desmethyl-PBB3 precursor for radiolabeling were synthesized from 5-bromo-2-nitropyridine, acrolein diethyl acetal, 6-methoxy-2-methylbenzothiazole, and diethylchlorophosphate with overall chemical yield 1% in six steps, 2% in five steps, and 1% in six steps, respectively. [11 C]PBB3 was prepared from either desmethyl-PBB3 or TBS-protected desmethyl-PBB3 with [11 C]CH 3 OTf through N-[ 11 C]methylation and isolated by HPLC combined with SPE in 20-25% and 15-20% radiochemical yield, respectively, based on [ 11 C]CO 2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity at EOB was 370-1110 GBq/mol with a total synthesis time of ~40-minutes from EOB.

show abstract

Development of Positron-Emission Tomography/Single-Photon Emission Computed Tomography Imaging Probes for in Vivo Detection of .BETA.-Amyloid Plaques in Alzheimer's Brains

Cited by 38 publications

References 51 publications

Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of Alzheimer’s Disease: Possible Involvement of HRD1, a Novel Molecule Related to Endoplasmic Reticulum Stress, in Alzheimer’s Disease

Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of Alzheimer’s Disease: Possible Involvement of HRD1, a Novel Molecule Related to Endoplasmic Reticulum Stress, in Alzheimer’s Disease

Rhodanine and Thiohydantoin Derivatives for Detecting Tau Pathology in Alzheimer’s Brains

Synthesis of a PET tau tracer [11C]PBB3 for imaging of Alzheimer’s disease

Contact Info

Product

Resources

About