Method Identifies When Parkinson’s Proteins Become Toxic to Brain Cells

Researchers have used a non-invasive method of observing how the process leading to Parkinson’s disease takes place at the nanoscale, and identified the point in the process at which proteins in the brain become toxic, eventually leading to the death of brain cells.

The results suggest that the same protein can either cause, or protect against, the toxic effects that lead to the death of brain cells, depending on the specific structural form it takes, and that toxic effects take hold when there is an imbalance of the level of protein in its natural form in a cell. The work could help unravel how and why people develop Parkinson’s, and aid in the search for potential treatments. The study is published in the journal Proceedings of the National Academy of Sciences.

Using super-resolution microscopy, researchers from the University of Cambridge were able to observe the behaviour of different types of alpha-synuclein, a protein closely associated with Parkinson’s disease, in order to find how it affects neurons, and at what point it becomes toxic.

Parkinson’s disease is one of a number of neurodegenerative diseases caused when naturally occurring proteins fold into the wrong shape and stick together with other proteins, eventually forming thin filament-like structures called amyloid fibrils. These amyloid deposits of aggregated alpha-synuclein, also known as Lewy bodies, are the hallmark of Parkinson’s disease.

Parkinson’s disease is the second-most common neurodegenerative disease worldwide (after Alzheimer’s disease). Close to 130,000 people in the UK, and more than seven million worldwide, have the disease. Symptoms include muscle tremors, stiffness and difficulty walking. Dementia is common in later stages of the disease.

“What hasn’t been clear is whether once alpha-synuclein fibrils have formed they are still toxic to the cell,” said Dr Dorothea Pinotsi of Cambridge’s Department of Chemical Engineering and Biotechnology, the paper’s first author.

Pinotsi and her colleagues from Cambridge’s Department of Chemical Engineering & Biotechnology and Department of Chemistry, and led by Dr Gabriele Kaminski Schierle, have used optical ‘super-resolution’ techniques to look into live neurons without damaging the tissue. “Now we can look at how proteins associated with neurodegenerative conditions grow over time, and how these proteins come together and are passed on to neighbouring cells,” said Pinotsi.

The researchers used different forms of alpha-synuclein and observed their behaviour in neurons from rats. They were then able to correlate what they saw with the amount of toxicity that was present.

They found that when they added alpha-synuclein fibrils to the neurons, they interacted with alpha-synuclein protein that was already in the cell, and no toxic effects were present.

“It was believed that amyloid fibrils that attack the healthy protein in the cell would be toxic to the cell,” said Pinotsi. “But when we added a different, soluble form of alpha-synuclein, it didn’t interact with the protein that was already present in the neuron and interestingly this was where we saw toxic effects and cells began to die. So somehow, when the soluble protein was added, it created this toxic effect. The damage appears to be done before visible fibrils are even formed.”

Image shows Lewy bodies in a brain slice.
Parkinson’s disease is one of a number of neurodegenerative diseases caused when naturally occurring proteins fold into the wrong shape and stick together with other proteins, eventually forming thin filament-like structures called amyloid fibrils. These amyloid deposits of aggregated alpha-synuclein, also known as Lewy bodies, are the hallmark of Parkinson’s disease. Credit: Dr. Andreas Becker.

The researchers then observed that by adding the soluble form of alpha-synuclein together with amyloid fibrils, the toxic effect of the former could be overcome. It appeared that the amyloid fibrils acted like magnets for the soluble protein and mopped up the soluble protein pool, shielding against the associated toxic effects.

“These findings change the way we look at the disease, because the damage to the neuron can happen when there is simply extra soluble protein present in the cell – it’s the excess amount of this protein that appears to cause the toxic effects that lead to the death of brain cells,” said Pinotsi. Extra soluble protein can be caused by genetic factors or ageing, although there is some evidence that it could also be caused by trauma to the head.

The research shows how important it is to fully understand the processes at work behind neurodegenerative diseases, so that the right step in the process can be targeted. “With these optical super-resolution techniques, we can really see details we couldn’t see before, so we may be able to counteract this toxic effect at an early stage,” said Pinotsi.

About this Parkinson’s disease research

Funding: The research was funded by the Medical Research Council, the Engineering and Physical Sciences Research Council, and the Wellcome Trust.

Source: Sarah Collins – University of Cambridge
Image Source: The image is credited to Dr. Andreas Becker and is licensed CC BY SA 3.0.
Original Research: The study will appear in PNAS during the week of March 14 2016.

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  1. Yes, Dr. Alan MacDonald has found some worldwide new cases with his DNA probes done on Alzheimer’s, dementia, MS, & Borrelia/Lyme/tick disease patients during his brain autopsies.

    My late husband, Jack Gordon, Iowa/USA, was diagnosed with essential tremors and then Parkinson’s disease 10 years ago prior to his sudden death 11.13.14.

    He was diagnosed with stage 4 cancer of r. lung/liver area 2 nights prior to his death; what a SHOCK!

    Jack is 1 of worldwide case discoveries of 2 diseases NEVER found together before on 11.22.2015:

    Lewy body dementia causing violent hallucinations and Borrelia/Lyme/tick disease.

    Jack had NEVER been diagnosed or treated for either of these diseases!

    Using his medical files, he was bitten by a tick 35 yrs. ago, and the drs. would never acknowledge it by diagnosing or treating him.

    Because he is the 1st case worldwide, we have written a scientific medical journal article in its final editing stages before it was PUBLISHED in an unknown, to me, journal in the very near future.

    My youngest brother’s wife, died of EARLY ONSET ALZHEIMERS at age 41; yes, 41 !! Mayo Clinic, Minn./USA, did her brain autopsy taking about 4 full months.

    Thank you for this article.

    Bettyg, IOWA / USA activist

  2. ALZHEIMERS integrating SIROCHETES biofilm & immune system

    A new paper out FEB. 2016 from a team at Drexel Univ, Philadelphia has confirmed DR. ALAN MACDONALD’S findings of bacterial biofilms co-localised with amyloid in brains of people with Alzheimers!

    The authors believe it is spirochaetes, although they did not use specific stains for borrelia.

    Also another paper will be out soon authored by Dr Tanzi providing further evidence that amyloid is an antimicrobial peptide.

    SEE poster board & photos are site! very interesting! bettyg


    Diversity of Forms- All Legitimate- All Borrelia forms and few to NONE are Corkscrew in form.

    DNA probe imaging results produce images of Borrelia in Diseased tissues Identical Borrelia.

    Images in Diseased tissues are produced with specific anti-borrelia staining techniques 9 Immuno-Histochemistry (IHC method) and all of these Non-Spiral forms are what actually appear in borrelia infected tissues.

    The Smallest forms “Dot Like” (Granular Borrelia) contain All of the INVECTIVE borrelia DNA needed to cause disease in the human host.

    Granular Borrelia (Dot-like) are the ONLY Borrelia living form which is present in the Bio-films of borrelia in Alzheimer’s Disease tissues; where the Biofilm borrelia communities are discovered beneath EACH and EVERY Amyloid Alzheimer’s Plaque in autopsy Brain studies.

    Dr. Rudolph Tanzi discovered in year 2010, by extraction of Amyloid from Autopsy Alzheimer’s Brains, that the purified Alz. Dis. Amyloid was ANTIBACTERIAL, and that the Amyloid in Alzheimer’s Disease is NON_TOXIC.

    In my biofilm Model, Each and every Amyloid Plaque in Every Alzheimer’s brain actually is doing its antibacterial job, by Coating the surfaces of the Biofilm communities of borrelia which lie beneath it.

    Link to lecture:


    Alan B. MacDonald, MD

    Fellow, College of American Pathologists

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