Inflammation and α-synuclein's prion-like behavior in Parkinson's disease--is there a link?

Carla M Lema Tomé,Stefan Grathwohl,Nolwen L Rey,Trevor Tyson,Markus Britschgi,Patrik Brundin

doi:10.1007/s12035-012-8267-8

Carla M Lema Tomé, Stefan Grathwohl + Show 4 more

Open Access

https://doi.org/10.1007/s12035-012-8267-8

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Abstract

Parkinson’s disease patients exhibit progressive spreading of aggregated α-synuclein in the nervous system. This slow process follows a specific pattern in an inflamed tissue environment. Recent research suggests that prion-like mechanisms contribute to the propagation of α-synuclein pathology. Little is known about factors that might affect the prion-like behavior of misfolded α-synuclein. In this review, we suggest that neuroinflammation plays an important role. We discuss causes of inflammation in the olfactory bulb and gastrointestinal tract and how this may promote the initial misfolding and aggregation of α-synuclein, which might set in motion events that lead to Parkinson's disease neuropathology. We propose that neuroinflammation promotes the prion-like behavior of α-synuclein and that novel anti-inflammatory therapies targeting this mechanism could slow disease progression.

Highlights

Age-related neurodegenerative disorders, including Parkinson’s disease (PD), are neuropathologically characterized by accumulation of misfolded proteins and the loss of neurons along with sustained neuroinflammation
In PD, they are located in neurons and are called Lewy bodies (LB) and Lewy neurites (LN) [4,5,6]
As discussed in this review, there is increasing evidence that α-syn aggregation may be initiated by a seeding mechanism that could spread throughout neurons in a prion-like fashion possibly involving other amyloidogenic proteins

Summary

Introduction

Age-related neurodegenerative disorders, including Parkinson’s disease (PD), are neuropathologically characterized by accumulation of misfolded proteins and the loss of neurons along with sustained neuroinflammation. Recent studies suggest that prion-like cell-to-cell transfer of possibly misfolded α-syn contributes to the spreading of neuropathology from one brain region to the [12,13,14,15,16,17]. As discussed in this review, there is increasing evidence that α-syn aggregation may be initiated by a seeding mechanism that could spread throughout neurons in a prion-like fashion possibly involving other amyloidogenic proteins.

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Conclusion