Volume 8 Issue 1
Feb.  2022
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Houfang Long, Shuyi Zeng, Dan Li. Cellular and animal models to investigate pathogenesis of amyloid aggregation in neurodegenerative diseases[J]. Biophysics Reports, 2022, 8(1): 14-28. doi: 10.52601/bpr.2022.210033
Citation: Houfang Long, Shuyi Zeng, Dan Li. Cellular and animal models to investigate pathogenesis of amyloid aggregation in neurodegenerative diseases[J]. Biophysics Reports, 2022, 8(1): 14-28. doi: 10.52601/bpr.2022.210033

Cellular and animal models to investigate pathogenesis of amyloid aggregation in neurodegenerative diseases

doi: 10.52601/bpr.2022.210033
Funds:  This work was supported by the Major State Basic Research Development Program (2019YFE0120600), the National Natural Science Foundation (NSF) of China (91853113 and 31872716), the Science and Technology Commission of Shanghai Municipality (STCSM) (18JC1420500, 20XD1425000 and 2019SHZDZX02), the “Eastern Scholar” project supported by the Shanghai Municipal Education Commission. Figures are created with BioRender.com. We acknowledge the resources provided by this website. HL summarized the protocol; HL and SZ carried out the experiments which formed the protocol, HL analyzed data and prepared figures; and HL, SZ and DL wrote the manuscript. All authors read and approved the final manuscript.
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  • Corresponding author: lidan2017@sjtu.edu.cn
  • Received Date: 30 July 2021
  • Accepted Date: 27 September 2021
  • Available Online: 21 January 2022
  • Publish Date: 28 February 2022
  • Abnormal aggregation of amyloid proteins, e.g. amyloid β (Aβ), Tau and α-synuclein (α-syn), is closely associated with a variety of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Cellular and animal models are useful to explore the neuropathology of amyloid aggregates in disease initiation and progression. In this protocol, we describe detailed procedures for how to establish neuronal and PD mouse models to evaluate amyloid pathologies including self-propagation, cell-to-cell transmission, neurotoxicity, and impact on mouse motor and cognitive functions. We use α-syn, a key pathogenic protein in PD, as an example to demonstrate the application of the protocol, while it can be used to investigate the pathologies of other amyloid proteins as well. The established disease models are also useful to assess the activities of drug candidates for therapeutics of neurodegenerative diseases.
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  • [1]
    Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H, Mann D, Tsuchiya K, Yoshida M, Hashizume Y, Oda T (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351(3): 602−611 doi: 10.1016/j.bbrc.2006.10.093
    [2]
    Baba M, Nakajo S, Tu PH, Tomita T, Nakaya K, Lee VM, Trojanowski JQ, Iwatsubo T (1998) Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies. Am J Pathol 152(4): 879−884
    [3]
    Damier P, Hirsch EC, Agid Y, Graybiel AM (1999) The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson's disease. Brain 122 ( Pt 8): 1437-1448
    [4]
    Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A (1988) Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc Natl Acad Sci USA 85(11): 4051−4055 doi: 10.1073/pnas.85.11.4051
    [5]
    Li Y, Zhao C, Luo F, Liu Z, Gui X, Luo Z, Zhang X, Li D, Liu C, Li X (2018) Amyloid fibril structure of alpha-synuclein determined by cryo-electron microscopy. Cell Res 28(9): 897−903 doi: 10.1038/s41422-018-0075-x
    [6]
    Long H, Zheng W, Liu Y, Sun Y, Zhao K, Liu Z, Xia W, Lv S, Liu Z, Li D, He KW, Liu C (2021) Wild-type alpha-synuclein inherits the structure and exacerbated neuropathology of E46K mutant fibril strain by cross-seeding. Proc Natl Acad Sci USA 118(20): e2012435118. https://doi.org/10.1073/pnas.2012435118
    [7]
    Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, Lee VM (2012) Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338(6109): 949−953 doi: 10.1126/science.1227157
    [8]
    Luk KC, Song C, O'Brien P, Stieber A, Branch JR, Brunden KR, Trojanowski JQ, Lee VM (2009) Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. Proc Natl Acad Sci USA 106(47): 20051−20056 doi: 10.1073/pnas.0908005106
    [9]
    Murphy MP, LeVine H, 3rd (2010) Alzheimer's disease and the amyloid-beta peptide. J Alzheimers Dis 19(1): 311−323 doi: 10.3233/JAD-2010-1221
    [10]
    Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388(6645): 839−840 doi: 10.1038/42166
    [11]
    Volpicelli-Daley LA, Luk KC, Lee VM (2014) Addition of exogenous alpha-synuclein preformed fibrils to primary neuronal cultures to seed recruitment of endogenous alpha-synuclein to Lewy body and Lewy neurite-like aggregates. Nat Protoc 9(9): 2135−2146 doi: 10.1038/nprot.2014.143
    [12]
    Zhang B, Kehm V, Gathagan R, Leight SN, Trojanowski JQ, Lee VM, Luk KC (2019) Stereotaxic Targeting of Alpha-Synuclein Pathology in Mouse Brain Using Preformed Fibrils. Methods Mol Biol 1948: 45−57
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