Tuesday, July 7, 2020

Circular Dichroism Spectroscopy Identifies the β-Adrenoceptor Agonist Salbutamol As a Direct Inhibitor of Tau Filament Formation in Vitro

You can ask your doctor what pieces of the kitchen sink they are throwing at preventing Alzheiners/dementia before clinical stuff is proven. 

Is this earlier research enough for your doctor to use?

Can An Anti-Asthma Drug Rejuvenate the Brain? montelukast January 2016 

A Decades-Old Asthma Drug Has Reversed Brain Damage From Dementia in Mice - zileuton July 2018

 

Or is your doctor using one of these to prevent dementia? 

1.  The End of Alzheimer's: The First Program to Prevent and Reverse Cognitive Decline by Dale Bredesen 

 

2.  A Real Alzheimer's Prevention Program from The University of California

 

3. I'm a Brain Doctor, and This Is What I Do to Prevent Alzheimer's December 2018 

 

4. Reversing the Alzheimer’s Catastrophe April 2007 

The latest here:

Circular Dichroism Spectroscopy Identifies the β-Adrenoceptor Agonist Salbutamol As a Direct Inhibitor of Tau Filament Formation in Vitro

  • David J Townsend*
  • Barbora Mala
  • Eleri Hughes
  • Rohanah Hussain
  • Giuliano Siligardi
  • Nigel J. Fullwood
  • , and 
  • David A. Middleton
Cite this: ACS Chem. Neurosci. 2020, XXXX, XXX, XXX-XXX
Publication Date:June 10, 2020
https://doi.org/10.1021/acschemneuro.0c00154
Copyright © 2020 American Chemical Society

Abstract

Abstract Image
Potential drug treatments for Alzheimer’s disease (AD) may be found by identifying compounds that block the assembly of the microtubule-associated protein tau into neurofibrillar tangles associated with neuron destabilization and cell death. Here, a small library of structurally diverse compounds was screened in vitro for the ability to inhibit tau aggregation, using high-throughput synchrotron radiation circular dichroism as a novel tool to monitor the structural changes in the protein as it assembles into filaments. The catecholamine epinephrine was found to be the most effective tau aggregation inhibitor of all 88 screened compounds. Subsequently, we tested chemically similar phenolamine drugs from the β-adrenergic receptor agonist class, using conventional circular dichroism spectroscopy, thioflavin T fluorescence, and transmission electron microscopy. Two compounds, salbutamol and dobutamine, used widely in the treatment of respiratory and cardiovascular disease, impede the aggregation of tau in vitro. Dobutamine reduces both the rate and yield of tau filament formation over 24 h; however, it has little effect on the structural transition of tau into β-sheet structures over 24 h. Salbutamol also reduces the yield and rate of filament formation and additionally inhibits tau’s structural change into β-sheet-rich aggregates. Salbutamol has a good safety profile and a half-life that facilitates permeation through the blood–brain barrier and could represent an expediated approach to developing AD therapeutics. These results provide the motivation for the in vivo evaluation of pre-existing β-adrenergic receptor agonists as a potential therapy for AD through the reduction of tau deposition.

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