The Experts below are selected from a list of 9114 Experts worldwide ranked by ideXlab platform
Makoto Hashimoto - One of the best experts on this subject based on the ideXlab platform.
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therapeutic potential of αs Evolvability for neuropathic gaucher disease
Biomolecules, 2021Co-Authors: Jianshe Wei, Yoshiki Takamatsu, Eliezer Masliah, Masayo Fujita, Ryoko Wada, Makoto HashimotoAbstract:Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by autosomal recessive mutations of the glucocerebrosidase gene, GBA1. In the majority of cases, GD has a non-neuropathic chronic form with adult onset (GD1), while other cases are more acute and severer neuropathic forms with early onset (GD2/3). Currently, no radical therapies are established for GD2/3. Notably, GD1, but not GD2/3, is associated with increased risk of Parkinson's disease (PD), the elucidation of which might provide a clue for novel therapeutic strategies. In this context, the objective of the present study is to discuss that the Evolvability of α-synuclein (αS) might be differentially involved in GD subtypes. Hypothetically, aging-associated PD features with accumulation of αS, and the autophagy-lysosomal dysfunction might be an antagonistic pleiotropy phenomenon derived from αS Evolvability in the development in GD1, without which neuropathies like GD2/3 might be manifested due to the autophagy-lysosomal dysfunction. Supposing that the increased severity of GD2/3 might be attributed to the decreased activity of αS Evolvability, suppressing the expression of β-synuclein (βS), a potential buffer against αS Evolvability, might be therapeutically efficient. Of interest, a similar view might be applicable to Niemann-Pick type C (NPC), another LSD, given that the adult type of NPC, which is comorbid with Alzheimer's disease, exhibits milder medical symptoms compared with those of infantile NPC. Thus, it is predicted that the Evolvability of amyloid β and tau, might be beneficial for the adult type of NPC. Collectively, a better understanding of amyloidogenic Evolvability in the pathogenesis of LSD may inform rational therapy development.
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motor and nonmotor symptoms of parkinson s disease antagonistic pleiotropy phenomena derived from α synuclein Evolvability
Parkinson's Disease, 2018Co-Authors: Yoshiki Takamatsu, Shuei Sugama, Takato Takenouchi, Masaaki Waragai, Eliezer Masliah, Masayo Fujita, Ryoko Wada, Makoto HashimotoAbstract: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.
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Evolvability and neurodegenerative disease antagonistic pleiotropy phenomena derived from amyloid aggregates
Journal of Parkinson's disease, 2018Co-Authors: Makoto Hashimoto, Yoshiki Takamatsu, Yuka Shimizu, Shuei Sugama, Takato Takenouchi, Masaaki Waragai, Eliezer MasliahAbstract:At present, the precise physiological role of neurodegenerative disease-related amyloidogenic proteins (APs), including α-synuclein in Parkinson's disease and β-amyloid in Alzheimer's disease, remains unclear. Because of similar adaptability of both human brain neurons and yeast cells to diverse environmental stressors, we previously proposed that the concept of Evolvability in yeast prion could also be applied to APs in human brain. However, the mechanistic relevance of Evolvability to neurodegenerative disorders is elusive. Therefore, our objective is to discuss our hypothesis that Evolvability and neurodegenerative disease may represent a form of antagonistic pleiotropy derived from the aggregates of APs. Importantly, such a perspective may provide an outlook of the entire course of sporadic neurodegenerative diseases.
Eliezer Masliah - One of the best experts on this subject based on the ideXlab platform.
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therapeutic potential of αs Evolvability for neuropathic gaucher disease
Biomolecules, 2021Co-Authors: Jianshe Wei, Yoshiki Takamatsu, Eliezer Masliah, Masayo Fujita, Ryoko Wada, Makoto HashimotoAbstract:Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by autosomal recessive mutations of the glucocerebrosidase gene, GBA1. In the majority of cases, GD has a non-neuropathic chronic form with adult onset (GD1), while other cases are more acute and severer neuropathic forms with early onset (GD2/3). Currently, no radical therapies are established for GD2/3. Notably, GD1, but not GD2/3, is associated with increased risk of Parkinson's disease (PD), the elucidation of which might provide a clue for novel therapeutic strategies. In this context, the objective of the present study is to discuss that the Evolvability of α-synuclein (αS) might be differentially involved in GD subtypes. Hypothetically, aging-associated PD features with accumulation of αS, and the autophagy-lysosomal dysfunction might be an antagonistic pleiotropy phenomenon derived from αS Evolvability in the development in GD1, without which neuropathies like GD2/3 might be manifested due to the autophagy-lysosomal dysfunction. Supposing that the increased severity of GD2/3 might be attributed to the decreased activity of αS Evolvability, suppressing the expression of β-synuclein (βS), a potential buffer against αS Evolvability, might be therapeutically efficient. Of interest, a similar view might be applicable to Niemann-Pick type C (NPC), another LSD, given that the adult type of NPC, which is comorbid with Alzheimer's disease, exhibits milder medical symptoms compared with those of infantile NPC. Thus, it is predicted that the Evolvability of amyloid β and tau, might be beneficial for the adult type of NPC. Collectively, a better understanding of amyloidogenic Evolvability in the pathogenesis of LSD may inform rational therapy development.
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motor and nonmotor symptoms of parkinson s disease antagonistic pleiotropy phenomena derived from α synuclein Evolvability
Parkinson's Disease, 2018Co-Authors: Yoshiki Takamatsu, Shuei Sugama, Takato Takenouchi, Masaaki Waragai, Eliezer Masliah, Masayo Fujita, Ryoko Wada, Makoto HashimotoAbstract: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.
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Evolvability and neurodegenerative disease antagonistic pleiotropy phenomena derived from amyloid aggregates
Journal of Parkinson's disease, 2018Co-Authors: Makoto Hashimoto, Yoshiki Takamatsu, Yuka Shimizu, Shuei Sugama, Takato Takenouchi, Masaaki Waragai, Eliezer MasliahAbstract:At present, the precise physiological role of neurodegenerative disease-related amyloidogenic proteins (APs), including α-synuclein in Parkinson's disease and β-amyloid in Alzheimer's disease, remains unclear. Because of similar adaptability of both human brain neurons and yeast cells to diverse environmental stressors, we previously proposed that the concept of Evolvability in yeast prion could also be applied to APs in human brain. However, the mechanistic relevance of Evolvability to neurodegenerative disorders is elusive. Therefore, our objective is to discuss our hypothesis that Evolvability and neurodegenerative disease may represent a form of antagonistic pleiotropy derived from the aggregates of APs. Importantly, such a perspective may provide an outlook of the entire course of sporadic neurodegenerative diseases.
Oystein H Opedal - One of the best experts on this subject based on the ideXlab platform.
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the Evolvability of animal pollinated flowers towards predicting adaptation to novel pollinator communities
New Phytologist, 2019Co-Authors: Oystein H OpedalAbstract:In the event of a community turnover, population decline, or complete disappearance of pollinators, animal-pollinated plants may respond by adapting to novel pollinators or by changing their mating system. The ability of populations to adapt is determined by their ability to respond to novel selection pressures, i.e. their Evolvability. In the short term, Evolvability is determined by standing genetic variation in the trait under selection. To evaluate the evolutionary potential of plant reproductive systems, I compiled genetic-variance estimates for a large selection of floral traits mediating shifts in pollination and mating systems. Then, I computed evolvabilities and compared these among trait groups and against the evolvabilities of vegetative traits. Evolvabilities of most floral traits were substantial yet tended to be lower than the median for vegetative traits. Among floral traits, herkogamy (anther–stigma distance), floral-display traits and perhaps floral-volatile concentrations had greater-than-average evolvabilities, while the evolvabilities of pollinator-fit traits were below average. These results suggest that most floral traits have the potential to evolve rapidly in response to novel selection pressures, providing resilience of plant reproductive systems in the event of changing pollinator communities. (Less)
Yoshiki Takamatsu - One of the best experts on this subject based on the ideXlab platform.
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therapeutic potential of αs Evolvability for neuropathic gaucher disease
Biomolecules, 2021Co-Authors: Jianshe Wei, Yoshiki Takamatsu, Eliezer Masliah, Masayo Fujita, Ryoko Wada, Makoto HashimotoAbstract:Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by autosomal recessive mutations of the glucocerebrosidase gene, GBA1. In the majority of cases, GD has a non-neuropathic chronic form with adult onset (GD1), while other cases are more acute and severer neuropathic forms with early onset (GD2/3). Currently, no radical therapies are established for GD2/3. Notably, GD1, but not GD2/3, is associated with increased risk of Parkinson's disease (PD), the elucidation of which might provide a clue for novel therapeutic strategies. In this context, the objective of the present study is to discuss that the Evolvability of α-synuclein (αS) might be differentially involved in GD subtypes. Hypothetically, aging-associated PD features with accumulation of αS, and the autophagy-lysosomal dysfunction might be an antagonistic pleiotropy phenomenon derived from αS Evolvability in the development in GD1, without which neuropathies like GD2/3 might be manifested due to the autophagy-lysosomal dysfunction. Supposing that the increased severity of GD2/3 might be attributed to the decreased activity of αS Evolvability, suppressing the expression of β-synuclein (βS), a potential buffer against αS Evolvability, might be therapeutically efficient. Of interest, a similar view might be applicable to Niemann-Pick type C (NPC), another LSD, given that the adult type of NPC, which is comorbid with Alzheimer's disease, exhibits milder medical symptoms compared with those of infantile NPC. Thus, it is predicted that the Evolvability of amyloid β and tau, might be beneficial for the adult type of NPC. Collectively, a better understanding of amyloidogenic Evolvability in the pathogenesis of LSD may inform rational therapy development.
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motor and nonmotor symptoms of parkinson s disease antagonistic pleiotropy phenomena derived from α synuclein Evolvability
Parkinson's Disease, 2018Co-Authors: Yoshiki Takamatsu, Shuei Sugama, Takato Takenouchi, Masaaki Waragai, Eliezer Masliah, Masayo Fujita, Ryoko Wada, Makoto HashimotoAbstract: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.
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Evolvability and neurodegenerative disease antagonistic pleiotropy phenomena derived from amyloid aggregates
Journal of Parkinson's disease, 2018Co-Authors: Makoto Hashimoto, Yoshiki Takamatsu, Yuka Shimizu, Shuei Sugama, Takato Takenouchi, Masaaki Waragai, Eliezer MasliahAbstract:At present, the precise physiological role of neurodegenerative disease-related amyloidogenic proteins (APs), including α-synuclein in Parkinson's disease and β-amyloid in Alzheimer's disease, remains unclear. Because of similar adaptability of both human brain neurons and yeast cells to diverse environmental stressors, we previously proposed that the concept of Evolvability in yeast prion could also be applied to APs in human brain. However, the mechanistic relevance of Evolvability to neurodegenerative disorders is elusive. Therefore, our objective is to discuss our hypothesis that Evolvability and neurodegenerative disease may represent a form of antagonistic pleiotropy derived from the aggregates of APs. Importantly, such a perspective may provide an outlook of the entire course of sporadic neurodegenerative diseases.
Masaaki Waragai - One of the best experts on this subject based on the ideXlab platform.
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motor and nonmotor symptoms of parkinson s disease antagonistic pleiotropy phenomena derived from α synuclein Evolvability
Parkinson's Disease, 2018Co-Authors: Yoshiki Takamatsu, Shuei Sugama, Takato Takenouchi, Masaaki Waragai, Eliezer Masliah, Masayo Fujita, Ryoko Wada, Makoto HashimotoAbstract: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.
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Evolvability and neurodegenerative disease antagonistic pleiotropy phenomena derived from amyloid aggregates
Journal of Parkinson's disease, 2018Co-Authors: Makoto Hashimoto, Yoshiki Takamatsu, Yuka Shimizu, Shuei Sugama, Takato Takenouchi, Masaaki Waragai, Eliezer MasliahAbstract:At present, the precise physiological role of neurodegenerative disease-related amyloidogenic proteins (APs), including α-synuclein in Parkinson's disease and β-amyloid in Alzheimer's disease, remains unclear. Because of similar adaptability of both human brain neurons and yeast cells to diverse environmental stressors, we previously proposed that the concept of Evolvability in yeast prion could also be applied to APs in human brain. However, the mechanistic relevance of Evolvability to neurodegenerative disorders is elusive. Therefore, our objective is to discuss our hypothesis that Evolvability and neurodegenerative disease may represent a form of antagonistic pleiotropy derived from the aggregates of APs. Importantly, such a perspective may provide an outlook of the entire course of sporadic neurodegenerative diseases.
