Parkinson's disease protein found in intestinal wall

[Conductor71]

The idea that Alpha-Syn is toxic is still a theory.

Widespread and abundant alpha-synuclein pathology in a neurologically unimpaired subject.
Parkkinen L, Pirttilä T, Tervahauta M, Alafuzoff I.
Source
Department of Neuroscience and Neurology, Kuopio University, Kuopio, Finland.

Abstract

The intracytoplasmic aggregation of alpha-synuclein (alphaS) protein is a common denominator for a group of neurodegenerative disorders currently known as synucleinopathies. It is generally assumed that the incorporation of alphaS protein into compact inclusions compromises the function and viability of its host cell via mechanical disruption. Herein, we report a widespread and abundant alphaS pathology in an elderly subject, whose medical history gave no indication of any neurodegenerative disease. We compared neuronal and glial components in this neurologically unimpaired subject with a patient with a clinical syndrome of dementia with Lewy bodies (DLB) by using a range of antigenic determinants and an in situ end-labeling technique. We detected no differences in vascular pathologies, in gliosis, or in apoptosis that would have explained the incompatible clinical end-points. With respect to the Alzheimer's disease-related changes, the only differences noted were the beta-amyloid aggregates in the putamen found in the DLB patient alone. Our findings suggest that there must be some currently unidentified factors rather than alphaS-positive inclusions that are responsible for the neuronal dysfunction. The alphaS-positive inclusions may well represent detoxified reserves that cells can tolerate for years, and thus prevention of their development could actually accelerate the diseases process.

PMID: 16382779 [PubMed - indexed for MEDLINE]

[lurkingforacure]

Originally Posted by Conductor71

The idea that Alpha-Syn is toxic is still a theory.

Widespread and abundant alpha-synuclein pathology in a neurologically unimpaired subject.
Parkkinen L, Pirttilä T, Tervahauta M, Alafuzoff I.
Source
Department of Neuroscience and Neurology, Kuopio University, Kuopio, Finland.

Abstract

The intracytoplasmic aggregation of alpha-synuclein (alphaS) protein is a common denominator for a group of neurodegenerative disorders currently known as synucleinopathies. It is generally assumed that the incorporation of alphaS protein into compact inclusions compromises the function and viability of its host cell via mechanical disruption. Herein, we report a widespread and abundant alphaS pathology in an elderly subject, whose medical history gave no indication of any neurodegenerative disease. We compared neuronal and glial components in this neurologically unimpaired subject with a patient with a clinical syndrome of dementia with Lewy bodies (DLB) by using a range of antigenic determinants and an in situ end-labeling technique. We detected no differences in vascular pathologies, in gliosis, or in apoptosis that would have explained the incompatible clinical end-points. With respect to the Alzheimer's disease-related changes, the only differences noted were the beta-amyloid aggregates in the putamen found in the DLB patient alone. Our findings suggest that there must be some currently unidentified factors rather than alphaS-positive inclusions that are responsible for the neuronal dysfunction. The alphaS-positive inclusions may well represent detoxified reserves that cells can tolerate for years, and thus prevention of their development could actually accelerate the diseases process.

PMID: 16382779 [PubMed - indexed for MEDLINE]

Thanks, Laura for this...while I love too the idea of this leading to a cure, I seem to remember something about an alz. drug that detangled the plaques and the patients got much worse....I wondered at that time if the plaques perhaps were forming as some kind of protective mechanism instead of the "cause" of the disease.

Also, have not several articles been written noting clumps of asyn in the brains of healthy people who had no symptoms of PD? And vice versa...people dx'd with PD did not have the clumps on autopsy?

I may have missed something, but I did not see where this finding was supported on the other side of the equation, that is, every PWP they looked at had the asyn in their gut....but also that no "normal" control (non PD) did not have the asyn.

By way of analogy, Jannetta's group had this balance: 78% of the PWP had compression in their brains, and only 2 of 20 non-PWP had compression (and one of those was dx's with PD the following year). It lends more credibility to the theory when the theory is supported on both sides, IMHO.

[indigogo]

Originally Posted by RLSmi

LFAC,
I've think people like Braak have suggested retrograde transport via nerves connecting the gut and brainstem such as the vagus. Also, movement between cells prion-like may be involved (e.g. across synapses; post-to-pre). Lewy bodies are already inside the BBB in gut ganglia.
Perhaps the real mystery is ...What causes aggregated alpha-syn to form in those ganglia in the first place?

Just to support what RLSmi is saying ........ Braak established systemic PD because of lewy bodies in the gut, etc, outside of the brain. That is one reason we know that PD is more than just dopamine neurotransmitters going wrong in the substantia nigra - its reach goes beyond a simple movement disorder.

The role of a-synuclein is not fully understood, whether toxic or friend, but it is generally thought to be of importance, maybe even the key, to understanding PD. MJFF, for one, is putting a lot of money on a-synuclein research.

[pegleg]

You are so right! There just seems to be no way that we can cure or even manage this disease until we identify the cause of misfolding proteins, why we have a lack of ability to penetrate the BBB, or where these malfunctions are taking place (mitochondria?, sibstantia nigra, globes palidus, intestinal wall, etc)

We somehow got away from the drive to identify the cause of our symptoms. Who knows; it could be that taking the meds exacerbates or creates our worsening symptoms? Otherwise, it is like looking for a needle in a haystack in our attempts at new therapies.

And what about the costs of these newer treatments? Duodopa is a prime example - I haven't confirmed it, but understand that one tube of the intestinal gel costs about $700 - that is ludicrous ! And that would not include the hardware (pump) or the pre-surgical prep!

Peg