Abstract：
:Genetic linkage studies and genome wide analysis have provided insights into complex medical diseases. Mycobacterium avium ss. paratuberculosis (MAP) causes Johne's disease, an important enteric inflammatory disease mostly studied in ruminant animals. MAP is also the putative cause of Crohn's disease. Moreover, MAP has been linked to other inflammatory diseases: sarcoidosis, Blau syndrome, autoimmune diabetes, autoimmune thyroiditis and multiple sclerosis. Genetic studies reveal an association between Parkinson's disease (PD), leprosy and Crohn's disease and since discovered, these findings have been considered "surprising". Autophagy and ubiquitin-proteosome systems are cellular systems that both fight intracellular pathogens (xenophagy) and maintain cellular protein quality control. PD is a common neurodegenerative disease that manifests clinically as a profound movement disorder. The recognized genetic defects of PD create disruption of cellular homeostasis that result in protein folding abnormalities of PD called Lewy bodies. Those same genetic defects are associated with susceptibility to intracellular pathogens, including mycobacteria. It is now understood that PD Lewy body pathology starts in the enteric nervous system and "spreads" to the brain in a retrograde fashion via the vagus nerve. This is the same process by which prions affect the brain. Lewy body pathology of the enteric nervous system predates the Lewy body pathology of the central nervous system (CNS) by years or even decades. This article proposes that genetic defects associated with PD also result in a permissive environment for MAP infection--ineffective xenophagy. It postulates that beginning as an enteric infection, MAP--via the vagus nerve--initiates a pathologic process that results in a targeted neuroinvasion of the CNS. The article proposes that MAP infection and resultant PD pathology are due, in the genetically at-risk and age dependant, to the consumptive exhaustion of the protein quality control systems.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Dow CTdoi
10.1016/j.mehy.2014.09.025subject
Has Abstractpub_date
2014-12-01 00:00:00pages
709-12issue
6eissn
0306-9877issn
1532-2777pii
S0306-9877(14)00350-8journal_volume
83pub_type
杂志文章abstract：:Most of the body iron is found within hemoglobin in red cells (the erythron), a smaller amount being distributed in other tissues such as muscles and in deposits. Iron homeostasis is a finely tuned process in which the most important regulators are probably the liver-derived hepcidin which blocks iron absorption and d...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2014.09.008
更新日期：2014-11-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2008.10.021
更新日期：2009-03-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(98)90201-8
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2003.12.059
更新日期：2005-01-01 00:00:00
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doi：10.1016/0306-9877(92)90115-s
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pub_type： 杂志文章
doi：10.1016/0306-9877(93)90133-b
更新日期：1993-02-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/j.mehy.2006.09.069
更新日期：2007-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章,评审
doi：10.1016/j.mehy.2019.03.010
更新日期：2019-05-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/0306-9877(94)90087-6
更新日期：1994-02-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2012.02.009
更新日期：2012-05-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2003.12.030
更新日期：2004-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(90)90099-z
更新日期：1990-08-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2004.10.018
更新日期：2005-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章,meta分析
doi：10.1016/j.mehy.2013.04.038
更新日期：2013-08-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2006.08.018
更新日期：2007-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2007.07.012
更新日期：2008-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2004.03.013
更新日期：2004-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 临床试验,杂志文章
doi：10.1016/j.mehy.2005.06.015
更新日期：2005-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(03)00072-0
更新日期：2003-06-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2020.110073
更新日期：2020-10-01 00:00:00
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pub_type： 历史文章,杂志文章
doi：10.1016/j.mehy.2009.12.012
更新日期：2010-05-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2015.06.025
更新日期：2015-10-01 00:00:00
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journal_title：Medical hypotheses
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doi：10.1016/j.mehy.2006.04.054
更新日期：2007-01-01 00:00:00
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更新日期：1985-08-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/j.mehy.2005.06.021
更新日期：2005-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章,评审
doi：10.1016/j.mehy.2011.08.005
更新日期：2011-11-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.1999.0920
更新日期：2000-04-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
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更新日期：2016-02-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/0306-9877(80)90104-8
更新日期：1980-05-01 00:00:00
