Speculating on a Viral Cause of Parkinson's Disease

Parkinson's disease is characterized by the progressive loss of a small population of dopamine-generating neurons in the brain. This loss happens to everyone, but progresses much faster and further in Parkinson's sufferers, for reasons that are still not fully understood. Here is a speculative paper in which researchers suggest that there are viral and autoimmune mechanisms at work:

Current concepts regarding the pathogenesis of Parkinson's disease support a model whereby environmental factors conspire with a permissive genetic background to initiate the disease. The identity of the responsible environmental trigger has remained elusive. There is incontrovertible evidence that aggregation of the neuronal protein alpha-synuclein is central to disease pathogenesis.

A novel hypothesis of Parkinson's pathogenesis implicates a pathogen acting in the olfactory mucosa and gastrointestinal tract as the inciting agent. In this point-of-view article, we hypothesize that α-synuclein aggregation in Parkinson's disease is an Epstein-Barr virus (EBV)-induced autoimmune phenomenon. Specifically, we have shown evidence for molecular mimicry between the C-terminal region of α-synuclein and a repeat region in the latent membrane protein 1 encoded by EBV.

We hypothesize that, in genetically-susceptible individuals, anti-EBV latent membrane protein antibodies targeting the critical repeat region cross react with the homologous epitope on α-synuclein and induce its oligomerization. We contend that axon terminals in the lamina propria of the gut are among the initial targets, with subsequent spread of pathology to the central nervous system. While at this time, we can only provide evidence from the literature and preliminary findings from our own laboratory, we hope that our hypothesis will stimulate the development of tractable experimental systems that can be exploited to test it. Further support for an EBV-induced immune pathogenesis for Parkinson's disease could have profound therapeutic implications.

Link: http://dx.doi.org/10.1016/j.parkreldis.2014.02.031


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