Possible Role of Amyloidogenic Evolvability in Dementia with Lewy Bodies: Insights from Transgenic Mice Expressing P123H β-Synuclein
Abstract
:1. Introduction
2. Comparison of the P123H βS Tg Mice with DLB
2.1. P123H βS Tg Mice
2.2. Other DLB Model Mice
3. Mechanism of DLB
3.1. Conventional View of the Mechanism of Neurodegeneration
3.2. Recent Hypothesis of the Mechanism of Neurodegeneration
4. DLB and Amyloidogenic Evolvability
4.1. Familial DLB
4.2. Sporadic DLB
4.3. Lewy Body Dementia and Amyloidogenic Evolvability
5. Therapy Implication
6. Conclusion
Author Contributions
Funding
Conflicts of Interest
Abbreviations
DLB | dementia with Lewy bodies |
S | synuclein |
Tg | transgenic |
AD | Alzheimer’s disease |
PD | Parkinson’s disease |
MSA | multiple system atrophy |
APs | amyloidogenic proteins |
GWAS | genome wide association studies |
GBA | glucocerebrocidase |
APOE | apolipoprotein E |
Aβ | amyloid β |
APP | amyloid precursor protein |
TGF | transforming growth factor |
IPSCs | induced pluripotent stem cells |
References
- Capouch, S.D.; Farlow, M.R.; Brosch, J.R. A Review of Dementia with Lewy Bodies’ Impact, Diagnostic Criteria and Treatment. Neurol. Ther. 2018, 7, 249–263. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hashimoto, M.; Masliah, E. Alpha-synuclein in Lewy body disease and Alzheimer’s disease. Brain Pathol. 1999, 9, 707–720. [Google Scholar] [CrossRef] [PubMed]
- Aarsland, D. Cognitive impairment in Parkinson’s disease and dementia with Lewy bodies. Parkinsonism Relat. Disord. 2016, 22 (Suppl. 1), S144–S148. [Google Scholar] [CrossRef] [PubMed]
- Ballard, C.G. Definition and diagnosis of dementia with Lewy bodies. Dement. Geriatr. Cogn. Disord. 2004, 17 (Suppl. 1), 15–24. [Google Scholar] [CrossRef] [PubMed]
- Heller, J.; Brcina, N.; Dogan, I.; Holtbernd, F.; Romanzetti, S.; Schulz, J.B.; Schiefer, J.; Reetz, K. Brain imaging findings in idiopathic REM sleep behavior disorder (RBD)—A systematic review on potential biomarkers for neurodegeneration. Sleep Med. Rev. 2017, 34, 23–33. [Google Scholar] [CrossRef] [PubMed]
- Joza, S.; Camicioli, R.; Ba, F. Falls in Synucleinopathies. Can. J. Neurol. Sci. 2019, 47, 30–43. [Google Scholar] [CrossRef] [PubMed]
- Zarranz, J.J.; Alegre, J.; Gomez-Esteban, J.C.; Lezcano, E.; Ros, R.; Ampuero, I.; Vidal, L.; Hoenicka, J.; Rodriguez, O.; Atares, B.; et al. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann. Neurol. 2004, 55, 164–173. [Google Scholar] [CrossRef]
- Ohtake, H.; Limprasert, P.; Fan, Y.; Onodera, O.; Kakita, A.; Takahashi, H.; Bonner, L.T.; Tsuang, D.W.; Murray, I.V.; Lee, V.M.; et al. Beta-synuclein gene alterations in dementia with Lewy bodies. Neurology 2004, 63, 805–811. [Google Scholar] [CrossRef]
- Wei, J.; Fujita, M.; Nakai, M.; Waragai, M.; Watabe, K.; Akatsu, H.; Rockenstein, E.; Masliah, E.; Hashimoto, M. Enhanced lysosomal pathology caused by beta-synuclein mutants linked to dementia with Lewy bodies. J. Biol. Chem. 2007, 282, 28904–28914. [Google Scholar] [CrossRef] [Green Version]
- Wei, J.; Fujita, M.; Nakai, M.; Waragai, M.; Sekigawa, A.; Sugama, S.; Takenouchi, T.; Masliah, E.; Hashimoto, M. Protective role of endogenous gangliosides for lysosomal pathology in a cellular model of synucleinopathies. Am. J. Pathol. 2009, 174, 1891–1909. [Google Scholar] [CrossRef] [Green Version]
- Hashimoto, M.; Ho, G.; Sugama, S.; Takamatsu, Y.; Shimizu, Y.; Takenouchi, T.; Waragai, M.; Masliah, E. Evolvability of Amyloidogenic Proteins in Human Brain. J. Alzheimer’s Dis. 2018, 62, 73–83. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hashimoto, M.; Ho, G.; Takamatsu, Y.; Shimizu, Y.; Sugama, S.; Takenouchi, T.; Waragai, M.; Masliah, E. Evolvability and Neurodegenerative Disease: Antagonistic Pleiotropy Phenomena Derived from Amyloid Aggregates. J. Parkinson’s Dis. 2018, 8, 405–408. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hashimoto, M.; Ho, G.; Takamatsu, Y.; Wada, R.; Sugama, S.; Takenouchi, T.; Masliah, E.; Waragai, M. Possible role of the polyglutamine elongation in evolution of amyloid-related evolvability. J. Huntingt. Dis. 2018, 7, 297–307. [Google Scholar] [CrossRef] [PubMed]
- Fujita, M.; Sugama, S.; Sekiyama, K.; Sekigawa, A.; Tsukui, T.; Nakai, M.; Waragai, M.; Takenouchi, T.; Takamatsu, Y.; Wei, J.; et al. A beta-synuclein mutation linked to dementia produces neurodegeneration when expressed in mouse brain. Nat. Commun. 2010, 1, 110. [Google Scholar] [CrossRef]
- Crabtree, D.M.; Zhang, J. Genetically engineered mouse models of Parkinson’s disease. Brain Res. Bull. 2012, 88, 13–32. [Google Scholar] [CrossRef] [Green Version]
- Galvin, J.E.; Uryu, K.; Lee, V.M.; Trojanowski, J.Q. Axon pathology in Parkinson’s disease and Lewy body dementia hippocampus contains alpha-, beta-, and gamma-synuclein. Proc. Natl. Acad. Sci. USA 1999, 96, 13450–13455. [Google Scholar] [CrossRef] [Green Version]
- Galvin, J.E.; Giasson, B.; Hurtig, H.I.; Lee, V.M.; Trojanowski, J.Q. Neurodegeneration with brain iron accumulation, type 1 is characterized by alpha-, beta-, and gamma-synuclein neuropathology. Am. J. Pathol. 2000, 157, 361–368. [Google Scholar] [CrossRef]
- Fujita, M.; Hagino, Y.; Takamatsu, Y.; Shimizu, Y.; Takamatsu, Y.; Ikeda, K.; Hashimoto, M. Early manifestation of depressive-like behavior in transgenic mice that express dementia with Lewy body-linked mutant beta-synuclein. Neuropsychopharmacol. Rep. 2018, 38, 95–97. [Google Scholar] [CrossRef]
- Mendoza-Velasquez, J.J.; Flores-Vazquez, J.F.; Barron-Velazquez, E.; Sosa-Ortiz, A.L.; Illigens, B.W.; Siepmann, T. Autonomic Dysfunction in alpha-Synucleinopathies. Front. Neurol. 2019, 10, 363. [Google Scholar] [CrossRef] [Green Version]
- Breitve, M.H.; Bronnick, K.; Chwiszczuk, L.J.; Hynninen, M.J.; Aarsland, D.; Rongve, A. Apathy is associated with faster global cognitive decline and early nursing home admission in dementia with Lewy bodies. Alzheimers Res. Ther. 2018, 10, 83. [Google Scholar] [CrossRef]
- Rockenstein, E.; Mallory, M.; Hashimoto, M.; Song, D.; Shults, C.W.; Lang, I.; Masliah, E. Differential neuropathological alterations in transgenic mice expressing alpha-synuclein from the platelet-derived growth factor and Thy-1 promoters. J. Neurosci. Res. 2002, 68, 568–578. [Google Scholar] [CrossRef] [PubMed]
- Kaufer, D. Dementia and Lewy bodies. Rev. Neurol. 2003, 37, 127–130. [Google Scholar] [PubMed]
- Hansen, L.A.; Galasko, D. Lewy body disease. Curr. Opin. Neurol. Neurosurg. 1992, 5, 889–894. [Google Scholar] [PubMed]
- Jellinger, K.A. Dementia with Lewy bodies and Parkinson’s disease-dementia: Current concepts and controversies. J. Neural. Transm. (Vienna) 2018, 125, 615–650. [Google Scholar] [CrossRef] [PubMed]
- Masliah, E.; Rockenstein, E.; Veinbergs, I.; Sagara, Y.; Mallory, M.; Hashimoto, M.; Mucke, L. beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer’s disease and Parkinson’s disease. Proc. Natl. Acad. Sci. USA 2001, 98, 12245–12250. [Google Scholar] [CrossRef] [Green Version]
- Emmer, K.L.; Waxman, E.A.; Covy, J.P.; Giasson, B.I. E46K human alpha-synuclein transgenic mice develop Lewy-like and tau pathology associated with age-dependent, detrimental motor impairment. J. Biol. Chem. 2011, 286, 35104–35118. [Google Scholar] [CrossRef] [Green Version]
- Kametani, F.; Hasegawa, M. Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer’s Disease. Front. Neurosci. 2018, 12, 25. [Google Scholar] [CrossRef] [Green Version]
- Takamatasu, Y.H.G.; Koike, W.; Sugama, S.; Takenouchi, T.; Waragai, M.; Wei, J.; Sekiyama, K.; Hashimoto, M. Combined immunotherapy with “anti-insulin resistance” therapy as a novel therapeutic strategy against neurodegenerative diseases. NPJ Parkinson’s Dis. 2017, 3, 1–10. [Google Scholar] [CrossRef] [Green Version]
- Pasqualetti, P.; Bonomini, C.; Dal Forno, G.; Paulon, L.; Sinforiani, E.; Marra, C.; Zanetti, O.; Rossini, P.M. A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer’s disease. Aging Clin. Exp. Res. 2009, 21, 102–110. [Google Scholar] [CrossRef]
- Green, R.C.; Schneider, L.S.; Amato, D.A.; Beelen, A.P.; Wilcock, G.; Swabb, E.A.; Zavitz, K.H.; Tarenflurbil Phase 3 Study, G. Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: A randomized controlled trial. JAMA 2009, 302, 2557–2564. [Google Scholar] [CrossRef] [Green Version]
- Sekiyama, K.; Fujita, M.; Sekigawa, A.; Takamatsu, Y.; Waragai, M.; Takenouchi, T.; Sugama, S.; Hashimoto, M. Ibuprofen ameliorates protein aggregation and astrocytic gliosis, but not cognitive dysfunction, in a transgenic mouse expressing dementia with Lewy bodies-linked P123H beta-synuclein. Neurosci. Lett. 2012, 515, 97–101. [Google Scholar] [CrossRef] [PubMed]
- Hsu, L.J.; Sagara, Y.; Arroyo, A.; Rockenstein, E.; Sisk, A.; Mallory, M.; Wong, J.; Takenouchi, T.; Hashimoto, M.; Masliah, E. Alpha-synuclein promotes mitochondrial deficit and oxidative stress. Am. J. Pathol. 2000, 157, 401–410. [Google Scholar] [CrossRef]
- Petersen, R.C.; Thomas, R.G.; Grundman, M.; Bennett, D.; Doody, R.; Ferris, S.; Galasko, D.; Jin, S.; Kaye, J.; Levey, A.; et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N. Engl. J. Med. 2005, 352, 2379–2388. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Eimer, W.A.; Vijaya Kumar, D.K.; Navalpur Shanmugam, N.K.; Rodriguez, A.S.; Mitchell, T.; Washicosky, K.J.; Gyorgy, B.; Breakefield, X.O.; Tanzi, R.E.; Moir, R.D. Alzheimer’s Disease-Associated beta-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection. Neuron 2018, 99, 56–63.e3. [Google Scholar] [CrossRef] [Green Version]
- Hashimoto, M.; Ho, G.; Takamatsu, Y.; Wada, R.; Sugama, S.; Takenouchi, T.; Waragai, M.; Masliah, E. Possible Role of Amyloid Cross-Seeding in Evolvability and Neurodegenerative Disease. J. Parkinsons Dis. 2019, 9, 793–802. [Google Scholar] [CrossRef] [Green Version]
- Takamatsu, Y.; Fujita, M.; Ho, G.J.; Wada, R.; Sugama, S.; Takenouchi, T.; Waragai, M.; Masliah, E.; Hashimoto, M. Motor and Nonmotor Symptoms of Parkinson’s Disease: Antagonistic Pleiotropy Phenomena Derived from alpha-Synuclein Evolvability? Parkinsons Dis. 2018, 2018, 5789424. [Google Scholar] [CrossRef] [Green Version]
- Polymeropoulos, M.H.; Lavedan, C.; Leroy, E.; Ide, S.E.; Dehejia, A.; Dutra, A.; Pike, B.; Root, H.; Rubenstein, J.; Boyer, R.; et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 1997, 276, 2045–2047. [Google Scholar] [CrossRef] [Green Version]
- Kruger, R.; Kuhn, W.; Muller, T.; Woitalla, D.; Graeber, M.; Kosel, S.; Przuntek, H.; Epplen, J.T.; Schols, L.; Riess, O. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson’s disease. Nat. Genet. 1998, 18, 106–108. [Google Scholar] [CrossRef]
- Fujioka, S.; Ogaki, K.; Tacik, P.M.; Uitti, R.J.; Ross, O.A.; Wszolek, Z.K. Update on novel familial forms of Parkinson’s disease and multiple system atrophy. Parkinsonism Relat. Disord. 2014, 20 (Suppl. 1), S29–S34. [Google Scholar] [CrossRef] [Green Version]
- Hashimoto, M.; Rockenstein, E.; Mante, M.; Mallory, M.; Masliah, E. beta-Synuclein inhibits alpha-synuclein aggregation: A possible role as an anti-parkinsonian factor. Neuron 2001, 32, 213–223. [Google Scholar] [CrossRef] [Green Version]
- Li, Y.; Li, P.; Liang, H.; Zhao, Z.; Hashimoto, M.; Wei, J. Gaucher-Associated Parkinsonism. Cell Mol. Neurobiol. 2015, 35, 755–761. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nalls, M.A.; Duran, R.; Lopez, G.; Kurzawa-Akanbi, M.; McKeith, I.G.; Chinnery, P.F.; Morris, C.M.; Theuns, J.; Crosiers, D.; Cras, P.; et al. A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies. JAMA Neurol. 2013, 70, 727–735. [Google Scholar] [CrossRef] [PubMed]
- Tsuang, D.; Leverenz, J.B.; Lopez, O.L.; Hamilton, R.L.; Bennett, D.A.; Schneider, J.A.; Buchman, A.S.; Larson, E.B.; Crane, P.K.; Kaye, J.A.; et al. APOE epsilon4 increases risk for dementia in pure synucleinopathies. JAMA Neurol. 2013, 70, 223–228. [Google Scholar] [CrossRef] [Green Version]
- Ma, J.; Yee, A.; Brewer, H.B., Jr.; Das, S.; Potter, H. Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein, E. promote assembly of Alzheimer beta-protein into filaments. Nature 1994, 372, 92–94. [Google Scholar] [CrossRef] [PubMed]
- George, J.M.; Jin, H.; Woods, W.S.; Clayton, D.F. Characterization of a novel protein regulated during the critical period for song learning in the zebra finch. Neuron 1995, 15, 361–372. [Google Scholar] [CrossRef] [Green Version]
- Lam, B.; Hollingdrake, E.; Kennedy, J.L.; Black, S.E.; Masellis, M. Cholinesterase inhibitors in Alzheimer’s disease and Lewy body spectrum disorders: The emerging pharmacogenetic story. Hum. Genom. 2009, 4, 91–106. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ubhi, K.; Inglis, C.; Mante, M.; Patrick, C.; Adame, A.; Spencer, B.; Rockenstein, E.; May, V.; Winkler, J.; Masliah, E. Fluoxetine ameliorates behavioral and neuropathological deficits in a transgenic model mouse of alpha-synucleinopathy. Exp. Neurol. 2012, 234, 405–416. [Google Scholar] [CrossRef] [Green Version]
- Cagnin, A.; Fragiacomo, F.; Camporese, G.; Turco, M.; Busse, C.; Ermani, M.; Montagnese, S. Sleep-Wake Profile in Dementia with Lewy Bodies, Alzheimer’s Disease, and Normal Aging. J. Alzheimers Dis. 2017, 55, 1529–1536. [Google Scholar] [CrossRef]
- Eisai Co., Ltd.; Biogen Inc. Biogen Plans Regulatory Filing for Aducanumab in Alzheimer’s Disease Based on New Analysis of Larger Dataset from Phase 3 Studies. Available online: http://www.eisai.com/news/2019/news201979.html (accessed on 22 October 2019).
- Tagliafierro, L.; Glenn, O.C.; Zamora, M.E.; Beach, T.G.; Woltjer, R.L.; Lutz, M.W.; Chiba-Falek, O. Genetic analysis of alpha-synuclein 3′ untranslated region and its corresponding microRNAs in relation to Parkinson’s disease compared to dementia with Lewy bodies. Alzheimers Dement. 2017, 13, 1237–1250. [Google Scholar] [CrossRef]
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Fujita, M.; Ho, G.; Takamatsu, Y.; Wada, R.; Ikeda, K.; Hashimoto, M. Possible Role of Amyloidogenic Evolvability in Dementia with Lewy Bodies: Insights from Transgenic Mice Expressing P123H β-Synuclein. Int. J. Mol. Sci. 2020, 21, 2849. https://doi.org/10.3390/ijms21082849
Fujita M, Ho G, Takamatsu Y, Wada R, Ikeda K, Hashimoto M. Possible Role of Amyloidogenic Evolvability in Dementia with Lewy Bodies: Insights from Transgenic Mice Expressing P123H β-Synuclein. International Journal of Molecular Sciences. 2020; 21(8):2849. https://doi.org/10.3390/ijms21082849
Chicago/Turabian StyleFujita, Masayo, Gilbert Ho, Yoshiki Takamatsu, Ryoko Wada, Kazutaka Ikeda, and Makoto Hashimoto. 2020. "Possible Role of Amyloidogenic Evolvability in Dementia with Lewy Bodies: Insights from Transgenic Mice Expressing P123H β-Synuclein" International Journal of Molecular Sciences 21, no. 8: 2849. https://doi.org/10.3390/ijms21082849