Motor and Nonmotor Symptoms of Parkinson’s Disease: Antagonistic Pleiotropy Phenomena Derived from α-Synuclein Evolvability?
Lewy body diseases, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are associated with a wide range of nonmotor symptoms (NMS), including cognitive impairment, depression and anxiety, sleep disorders, gastrointestinal symptoms, and autonomic fai...
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doaj-d2607008c6b54a669ae5af79954ac3f52020-11-25T01:40:05ZengHindawi LimitedParkinson's Disease2090-80832042-00802018-01-01201810.1155/2018/57894245789424Motor and Nonmotor Symptoms of Parkinson’s Disease: Antagonistic Pleiotropy Phenomena Derived from α-Synuclein Evolvability?Yoshiki Takamatsu0Masayo Fujita1Gilbert J. Ho2Ryoko Wada3Shuei Sugama4Takato Takenouchi5Masaaki Waragai6Eliezer Masliah7Makoto Hashimoto8Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, JapanTokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, JapanPCND Neuroscience Research Institute, Poway, CA, USATokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, JapanDepartment of Physiology, Nippon Medical School, Tokyo, JapanInstitute of Agrobiological Sciences, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, JapanTokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, JapanDepartment of Neuroscience, National Institute on Aging, Bethesda, MD 20892, USATokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, JapanLewy body diseases, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are associated with a wide range of nonmotor symptoms (NMS), including cognitive impairment, depression and anxiety, sleep disorders, gastrointestinal symptoms, and autonomic failure. The reason why such diverse and disabling NMS have not been weeded out but have persisted across evolution is unknown. As such, one possibility would be that the NMS might be somehow beneficial during development and/or reproductive stages, a possibility consistent with our recent view as to the evolvability of amyloidogenic proteins (APs) such as α-synuclein (αS) and amyloid-β (Aβ) in the brain. Based on the heterogeneity of protofibrillar AP forms in terms of structure and cytotoxicity, we recently proposed that APs might act as vehicles to deliver information regarding diverse internal and environmental stressors. Also, we defined evolvability to be an epigenetic phenomenon whereby APs are transgenerationally transmitted from parents to offspring to cope with future brain stressors in the offspring, likely benefitting the offspring. In this context, the main objective is to discuss whether NMS might be relevant to evolvability. According to this view, information regarding NMS may be transgenerationally transmitted by heterogeneous APs to offspring, preventing or attenuating the stresses related to such symptoms. On the other hand, NMS associated with Lewy body pathology might manifest through an aging-associated antagonistic pleiotropy mechanism. Given that NMS are not only specific to Lewy body diseases but also displayed in other disorders, including amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD), these conditions might share common mechanisms related to evolvability. This might give insight into novel therapy strategies based on antagonistic pleiotropy rather than on individual NMS from which to develop disease-modifying therapies.http://dx.doi.org/10.1155/2018/5789424 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yoshiki Takamatsu Masayo Fujita Gilbert J. Ho Ryoko Wada Shuei Sugama Takato Takenouchi Masaaki Waragai Eliezer Masliah Makoto Hashimoto |
spellingShingle |
Yoshiki Takamatsu Masayo Fujita Gilbert J. Ho Ryoko Wada Shuei Sugama Takato Takenouchi Masaaki Waragai Eliezer Masliah Makoto Hashimoto Motor and Nonmotor Symptoms of Parkinson’s Disease: Antagonistic Pleiotropy Phenomena Derived from α-Synuclein Evolvability? Parkinson's Disease |
author_facet |
Yoshiki Takamatsu Masayo Fujita Gilbert J. Ho Ryoko Wada Shuei Sugama Takato Takenouchi Masaaki Waragai Eliezer Masliah Makoto Hashimoto |
author_sort |
Yoshiki Takamatsu |
title |
Motor and Nonmotor Symptoms of Parkinson’s Disease: Antagonistic Pleiotropy Phenomena Derived from α-Synuclein Evolvability? |
title_short |
Motor and Nonmotor Symptoms of Parkinson’s Disease: Antagonistic Pleiotropy Phenomena Derived from α-Synuclein Evolvability? |
title_full |
Motor and Nonmotor Symptoms of Parkinson’s Disease: Antagonistic Pleiotropy Phenomena Derived from α-Synuclein Evolvability? |
title_fullStr |
Motor and Nonmotor Symptoms of Parkinson’s Disease: Antagonistic Pleiotropy Phenomena Derived from α-Synuclein Evolvability? |
title_full_unstemmed |
Motor and Nonmotor Symptoms of Parkinson’s Disease: Antagonistic Pleiotropy Phenomena Derived from α-Synuclein Evolvability? |
title_sort |
motor and nonmotor symptoms of parkinson’s disease: antagonistic pleiotropy phenomena derived from α-synuclein evolvability? |
publisher |
Hindawi Limited |
series |
Parkinson's Disease |
issn |
2090-8083 2042-0080 |
publishDate |
2018-01-01 |
description |
Lewy body diseases, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are associated with a wide range of nonmotor symptoms (NMS), including cognitive impairment, depression and anxiety, sleep disorders, gastrointestinal symptoms, and autonomic failure. The reason why such diverse and disabling NMS have not been weeded out but have persisted across evolution is unknown. As such, one possibility would be that the NMS might be somehow beneficial during development and/or reproductive stages, a possibility consistent with our recent view as to the evolvability of amyloidogenic proteins (APs) such as α-synuclein (αS) and amyloid-β (Aβ) in the brain. Based on the heterogeneity of protofibrillar AP forms in terms of structure and cytotoxicity, we recently proposed that APs might act as vehicles to deliver information regarding diverse internal and environmental stressors. Also, we defined evolvability to be an epigenetic phenomenon whereby APs are transgenerationally transmitted from parents to offspring to cope with future brain stressors in the offspring, likely benefitting the offspring. In this context, the main objective is to discuss whether NMS might be relevant to evolvability. According to this view, information regarding NMS may be transgenerationally transmitted by heterogeneous APs to offspring, preventing or attenuating the stresses related to such symptoms. On the other hand, NMS associated with Lewy body pathology might manifest through an aging-associated antagonistic pleiotropy mechanism. Given that NMS are not only specific to Lewy body diseases but also displayed in other disorders, including amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD), these conditions might share common mechanisms related to evolvability. This might give insight into novel therapy strategies based on antagonistic pleiotropy rather than on individual NMS from which to develop disease-modifying therapies. |
url |
http://dx.doi.org/10.1155/2018/5789424 |
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