Pros and cons of a prion-like pathogenesis in Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder which affects widespread areas of the brainstem, basal ganglia and cerebral cortex. A number of proteins are known to accumulate in parkinsonian brains...

Full description

Bibliographic Details
Main Authors: Brotchie Jonathan M, Hilker Ruediger, Chapman Joab
Format: Article
Language:English
Published: BMC 2011-06-01
Series:BMC Neurology
Online Access:http://www.biomedcentral.com/1471-2377/11/74
id doaj-c14e1e75e970462fb732d06a844d7874
record_format Article
spelling doaj-c14e1e75e970462fb732d06a844d78742020-11-24T21:52:52ZengBMCBMC Neurology1471-23772011-06-011117410.1186/1471-2377-11-74Pros and cons of a prion-like pathogenesis in Parkinson's diseaseBrotchie Jonathan MHilker RuedigerChapman Joab<p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder which affects widespread areas of the brainstem, basal ganglia and cerebral cortex. A number of proteins are known to accumulate in parkinsonian brains including ubiquitin and α-synuclein. Prion diseases are sporadic, genetic or infectious disorders with various clinical and histopathological features caused by prion proteins as infectious proteinaceous particles transmitting a misfolded protein configuration through brain tissue. The most important form is Creutzfeldt-Jakob disease which is associated with a self-propagating pathological precursor form of the prion protein that is physiologically widely distributed in the central nervous system.</p> <p>Discussion</p> <p>It has recently been found that α-synuclein may behave similarly to the prion precursor and propagate between cells. The post-mortem proof of α-synuclein containing Lewy bodies in embryonic dopamine cells transplants in PD patient suggests that the misfolded protein might be transmitted from the diseased host to donor neurons reminiscent of prion behavior. The involvement of the basal ganglia and brainstem in the degenerative process are other congruencies between Parkinson's and Creutzfeldt-Jakob disease. However, a number of issues advise caution before categorizing Parkinson's disease as a prion disorder, because clinical appearance, brain imaging, cerebrospinal fluid and neuropathological findings exhibit fundamental differences between both disease entities. Most of all, infectiousness, a crucial hallmark of prion diseases, has never been observed in PD so far. Moreover, the cellular propagation of the prion protein has not been clearly defined and it is, therefore, difficult to assess the molecular similarities between the two disease entities.</p> <p>Summary</p> <p>At the current state of knowledge, the molecular pathways of transmissible pathogenic proteins are not yet fully understood. Their exact involvement in the pathophysiology of prion disorders and neurodegenerative diseases has to be further investigated in order to elucidate a possible overlap between both disease categories that are currently regarded as distinct entities.</p> http://www.biomedcentral.com/1471-2377/11/74
collection DOAJ
language English
format Article
sources DOAJ
author Brotchie Jonathan M
Hilker Ruediger
Chapman Joab
spellingShingle Brotchie Jonathan M
Hilker Ruediger
Chapman Joab
Pros and cons of a prion-like pathogenesis in Parkinson's disease
BMC Neurology
author_facet Brotchie Jonathan M
Hilker Ruediger
Chapman Joab
author_sort Brotchie Jonathan M
title Pros and cons of a prion-like pathogenesis in Parkinson's disease
title_short Pros and cons of a prion-like pathogenesis in Parkinson's disease
title_full Pros and cons of a prion-like pathogenesis in Parkinson's disease
title_fullStr Pros and cons of a prion-like pathogenesis in Parkinson's disease
title_full_unstemmed Pros and cons of a prion-like pathogenesis in Parkinson's disease
title_sort pros and cons of a prion-like pathogenesis in parkinson's disease
publisher BMC
series BMC Neurology
issn 1471-2377
publishDate 2011-06-01
description <p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder which affects widespread areas of the brainstem, basal ganglia and cerebral cortex. A number of proteins are known to accumulate in parkinsonian brains including ubiquitin and α-synuclein. Prion diseases are sporadic, genetic or infectious disorders with various clinical and histopathological features caused by prion proteins as infectious proteinaceous particles transmitting a misfolded protein configuration through brain tissue. The most important form is Creutzfeldt-Jakob disease which is associated with a self-propagating pathological precursor form of the prion protein that is physiologically widely distributed in the central nervous system.</p> <p>Discussion</p> <p>It has recently been found that α-synuclein may behave similarly to the prion precursor and propagate between cells. The post-mortem proof of α-synuclein containing Lewy bodies in embryonic dopamine cells transplants in PD patient suggests that the misfolded protein might be transmitted from the diseased host to donor neurons reminiscent of prion behavior. The involvement of the basal ganglia and brainstem in the degenerative process are other congruencies between Parkinson's and Creutzfeldt-Jakob disease. However, a number of issues advise caution before categorizing Parkinson's disease as a prion disorder, because clinical appearance, brain imaging, cerebrospinal fluid and neuropathological findings exhibit fundamental differences between both disease entities. Most of all, infectiousness, a crucial hallmark of prion diseases, has never been observed in PD so far. Moreover, the cellular propagation of the prion protein has not been clearly defined and it is, therefore, difficult to assess the molecular similarities between the two disease entities.</p> <p>Summary</p> <p>At the current state of knowledge, the molecular pathways of transmissible pathogenic proteins are not yet fully understood. Their exact involvement in the pathophysiology of prion disorders and neurodegenerative diseases has to be further investigated in order to elucidate a possible overlap between both disease categories that are currently regarded as distinct entities.</p>
url http://www.biomedcentral.com/1471-2377/11/74
work_keys_str_mv AT brotchiejonathanm prosandconsofaprionlikepathogenesisinparkinsonsdisease
AT hilkerruediger prosandconsofaprionlikepathogenesisinparkinsonsdisease
AT chapmanjoab prosandconsofaprionlikepathogenesisinparkinsonsdisease
_version_ 1725874355814006784