“In current models of neurodegeneration, individual diseases are defined by the presence of one or two pathogenic protein species. Yet, it is the rule rather than the exception that a patient meets criteria for more than one disease”
These are the first lines of a manuscript on the preprint sharing webiste BioRxiv, which analysed the co-occurance of biological markers of Alzheimer’s or Parkinson’s or other neurodegenerative conditions across 18 brain regions in 1389 postmortem brain from people who passed away with a neurodegenerative condition.
The results are interesting.
In today’s post, we will discuss what this study did, what is meant by “transdiagnostic disease clusters”, and consider what could they mean for our understanding of Parkinson’s… and heck, neurodegenerative conditions in general.
Malcolm Gladwell. Source: Masterclass
I am a fan of Malcolm Gadwell (not an endorsement, this is just me sharing).
He has a great way of looking at a situation from a completely different angle, finding things that no one else sees, and then writing about it in a clever, easy to read manner. Having read most of his books, I was rather pleased to learn that he has a podcast – Revisionist History.
And it’s good.
Oh boy, it’s good.
The first episodes of the most recent series of the podcast have helped to raise my fragile self esteem, because I am definitely a tortoise (just listen to the first two episodes of season 4 and you’ll understand).
Oh, and Mr Gladwell, if you ever read this – in the next series of the podcast, please have a look at the dysfunctional way we clinically test new therapies in medicine – click here to read a previous SoPD rant on this topic. Thanks!
What does Malcolm Gladwell have to do with Parkinson’s?
It all comes back to that idea of looking at a situation from a completely different angle.
What do you mean?
Recently I wrote a post about research investigating an interesting compound called Epigallocatechin gallate (or EGCG – click here for that post). Several eagle-eyed readers, however, noted something interesting in the details of one of the research reports that was discussed in that post.
The study in question had used EGCG as a positive control for evaluating the ability of other compounds for their ability to inhibit the clustering of Parkinson’s-associated protein alpha synuclein.
But there was also a second positive control used in that study.
It is called baicalein.
In today’s post, we will discuss what baicalein is and what research has been done on it in the context of Parkinson’s.
Lake Baikal. Source: Audleytravel
Once upon a thyme, in a far away land, there was a mysterious little flowering plant.
The “far away land” was the southern parts of eastern Siberia.
And the flowering plant is Scutellaria baicalensis – which is more commonly referred to as Baikal skullcap.
What is Baikal skullcap?
Baikal skullcap is a perennial herb that is indigenous to Southern Siberia, China and Korea. For centuries, traditional Chinese medicine has used the dried roots – which is called huángqín (Chinese: 黄芩 or golden root) – for a variety of ailments.
Baikal skullcap. Source: Urbol
The plant grows to between 1-4 feet in height, with lance head-shaped leaves and blue-purple flowers. Baikal skullcap belongs to the same family of flowering plants (Lamiaceae) as thyme, basil, mint and rosemary.
For traditional Chinese medicinal use, the roots are usually collected in spring or autumn once the plant is more than 3-4 years old. They are dried and then used to treat hypertension, to reduce “fire and dampness”, and to treat prostate & breast cancers.
And one of the key constituents of Baikal skullcap (and huángqín) is a compound called baicalein.
What is baicalein?
Trehalose is a small molecule – nutritionally equivalent to glucose – that helps to prevent protein from aggregating (that is, clustering together in a bad way).
Parkinson’s disease is a neurodegenerative condition that is characterised by protein aggregating, or clustering together in a bad way.
Is anyone else thinking what I’m thinking?
In today’s post we will look at what trelahose is, review some of the research has been done in the context of Parkinson’s disease, and discuss how we should be thinking about assessing this molecule clinically.
Neuropathologists examining a section of brain tissue. Source: Imperial
When a neuropathologist makes an examination of the brain of a person who passed away with Parkinson’s, there are two characteristic hallmarks that they will be looking for in order to provide a definitively postmortem diagnosis of the condition:
1. The loss of dopamine producing neurons in a region of the brain called the substantia nigra.
The dark pigmented dopamine neurons in the substantia nigra are reduced in the Parkinson’s disease brain (right). Source:Memorangapp
2. The clustering (or ‘aggregation’) of a protein called alpha synuclein. Specifically, they will be looking for dense circular aggregates of the protein within cells, which are referred to as Lewy bodies.
A Lewy body inside of a neuron. Source: Neuropathology-web
A cartoon of a neuron, with the Lewy body indicated within the cell body. Source: Alzheimer’s news
In addition to Lewy bodies, the neuropathologist may also see alpha synuclein clustering in other parts of affected cells. For example, aggregated alpha synuclein can be seen in the branches of cells (these clusterings are called ‘Lewy neurites‘ – see the image below where alpha synuclein has been stained brown on a section of brain from a person with Parkinson’s disease.
Examples of Lewy neurites (indicated by arrows). Source: Wikimedia
Given these two distinctive features of the Parkinsonian brain (the loss of dopamine neurons and the aggregation of alpha synuclein), a great deal of research has focused on A.) neuroprotective agents to protect the remaining dopamine-producing neurons in the substantia nigra, and B.) compounds that stop the aggregation of alpha synuclein.
In today’s post, we will look at the research that has been conducted on one particular compounds that appears to stop the aggregation of alpha synuclein.
It is call Trehalose (pronounces ‘tray-hellos’).