New evidence supports the ring theory of Parkinson’s disease



University of California, San Diego researchers (CA, USA) have provided a sequential molecular explanation for α-synuclein (α-syn) oligomerization; the study supports the role of pore-like structures in neuronal membranes in the pathogenesis of Parkinson’s disease (PD).

PD and dementia with Lewy bodies
... are characterized by a progressive accumulation of α-syn in the CNS. However, the underlying mechanisms leading to and resulting from this protein aggregation have not yet been elucidated.

The study... describes how α-syn monomers rapidly penetrate cell membranes, become coiled and aggregate into ring-like structures that are thought to be responsible for neuronal toxicity in PD. It is thought that many ring structures would be necessary to kill resilient neurons; however, at some point, the assault proves too great and neuronal repair cannot compete. Thus, the symptoms of PD gradually worsen.

“We think we can create drugs to give us an anti-Parkinson’s effect by slowing the formation and growth of these ring structures,” ...

The A53T mutation is commonly associated with familial PD. Through computer modeling and cell-based studies, the team investigated the membrane-based oligomerization process, which occurred more rapidly for the A53T mutant α-syn compared with wild-type α-syn. Following 9 ns of stimulation, oligomer penetration resulted in a pore-like hole in the membrane. Mutant α-syn demonstrated a greater tendency to accumulate in neuronal membranes, thus resulting in greater permeability.

These results controversially support a once-marginalized theory for PD and conflict with the belief that insoluble intracellular fibrils, or amyloids, are the underlying cause of PD. “The most dangerous assault on the neurons of PD patients appears to be the relatively small α-syn ring structures themselves,” ...
“It was once heretical to suggest that these ring structures, rather than long fibrils found in neurons of people having PD, were responsible for the symptoms of the disease...– Written by Sarah Freeston

Source: Tsigelny IF, Sharikov Y, Wrasidlo W et al. Role of α-synuclein penetration into the membrane in the mechanisms of oligomer pore formation. FEBS J. 279(6), 1000–1013 (2012).
http://www.futuremedicine.com/doi/fu...2217/nmt.12.33

Olsen, I posted this info already last week. See my "once-marginalized theory" thread.

AHHH, that is where I recently read about this not new theory being re examined. frequently, with all the research/reading/attempting to synthesize massive amounts of info, posters (ie me) will repost something that is already on the forum. In my case it is due to overload. madelyn