Deans' stroke musings: Rational Design of a Theranostic Agent Triggered by Endogenous Nitric Oxide in a Cellular Model of Alzheimer’s Disease

Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Saturday, June 25, 2022

Rational Design of a Theranostic Agent Triggered by Endogenous Nitric Oxide in a Cellular Model of Alzheimer’s Disease

What does this mean for all the benefits of getting nitric oxide?

nitric oxide (107 posts to March 2011)

Ask your doctor for a specific analysis. I can't figure out what upregulated is.

Pathogenesis: the manner of development of a disease.

Rational Design of a Theranostic Agent Triggered by Endogenous Nitric Oxide in a Cellular Model of Alzheimer’s Disease

Kang Lu

Yu Wang

Hao Zhang

Cuiqing Tian

Wenxiang Wang

Tian Yang

Baiwen Qi

, and

Song Wu*

Cite this: J. Med. Chem. 2022, XXXX, XXX, XXX-XXX

Publication Date:June 21, 2022

https://doi.org/10.1021/acs.jmedchem.2c00399

Abstract

Oxidative damage caused by upregulated nitric oxide (NO) plays an important role in the pathogenesis of Alzheimer’s disease (AD). Currently, stimulus-triggered theranostic agents have received much attention due to benefits on disease imaging and targeted therapeutic effects. However, the development of a theranostic agent triggered by NO for AD remains unexplored. Herein, through the mechanism analysis of the reaction between a fluorophore of 9,14-diphenyl-9,14-dihydrodibenzo[a,c]phenazine (DPAC) and NO, which we occasionally found and thereafter structure optimization of DPAC, a theranostic agent DPAC-(peg)₄-memantine was fabricated. In an AD cellular model, DPAC-(peg)₄-memantine exhibits NO sensing ability for AD imaging. Meanwhile, DPAC-(peg)₄-memantine shows improved therapeutic by targeted drug release triggered by NO and sustained therapeutic effects owing to the synergetic antioxidative abilities via the anti-AD drug and NO scavenging. This work provides an unprecedented avenue for the studies on not only AD but also other diseases with NO upregulation.

Supporting Information

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jmedchem.2c00399.

Molecular formula strings (CSV)
The proposed reaction mechanism of DPAC with NO; NMR, HRMS, and HPLC analysis of the reaction mechanism; detection limit of DPAC-(peg)₄-memantine with NO; the parallel artificial membrane permeability assay (PAMPA) of DPAC-(peg)₄-memantine; time-dependent effects of DPAC-(peg)₄-memantine and the related drugs on HT22 cells under the coculture system; the LIVE/DEAD staining of HT22 cells under the coculture system with 9,10-PAQ and p-benzoquinone; Glu release on HT22 cells under the coculture system with HO-(peg)₄-memantine and memantine¹; and H,¹³C NMR, and HRMS spectra of the products (PDF)