دورية أكاديمية
أعرض في EDS

Toxic properties of microsome-associated alpha-synuclein species in mouse primary neurons.

التفاصيل البيبلوغرافية
العنوان: Toxic properties of microsome-associated alpha-synuclein species in mouse primary neurons.
المؤلفون: Colla E; Bio@SNS Laboratory, Scuola Normale Superiore, Pisa, Italy. Electronic address: emanuela.colla@sns.it., Panattoni G; Bio@SNS Laboratory, Scuola Normale Superiore, Pisa, Italy., Ricci A; Bio@SNS Laboratory, Scuola Normale Superiore, Pisa, Italy., Rizzi C; Bio@SNS Laboratory, Scuola Normale Superiore, Pisa, Italy., Rota L; Bio@SNS Laboratory, Scuola Normale Superiore, Pisa, Italy., Carucci N; Bio@SNS Laboratory, Scuola Normale Superiore, Pisa, Italy., Valvano V; Bio@SNS Laboratory, Scuola Normale Superiore, Pisa, Italy., Gobbo F; Bio@SNS Laboratory, Scuola Normale Superiore, Pisa, Italy., Capsoni S; Bio@SNS Laboratory, Scuola Normale Superiore, Pisa, Italy., Lee MK; Department of Neuroscience, University of Minnesota, United States; Institute for Translational Neuroscience, University of Minnesota, United States., Cattaneo A; Bio@SNS Laboratory, Scuola Normale Superiore, Pisa, Italy; Neurotrophins and Neurodegenerative Diseases Laboratory, Rita Levi-Montalcini European Brain Research Institute, Rome, Italy.
المصدر: Neurobiology of disease [Neurobiol Dis] 2018 Mar; Vol. 111, pp. 36-47. Date of Electronic Publication: 2017 Dec 12.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Academic Press Country of Publication: United States NLM ID: 9500169 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-953X (Electronic) Linking ISSN: 09699961 NLM ISO Abbreviation: Neurobiol Dis Subsets: MEDLINE
أسماء مطبوعة: Publication: San Diego, CA : Academic Press
Original Publication: Oxford : Blackwell Science, c1994-
مواضيع طبية MeSH: Endoplasmic Reticulum/*metabolism , Microsomes/*metabolism , Neurons/*metabolism , Protein Aggregation, Pathological/*metabolism , alpha-Synuclein/*metabolism, Animals ; Apoptosis/physiology ; Cell Line, Tumor ; Cerebral Cortex/metabolism ; Cerebral Cortex/pathology ; Disease Models, Animal ; Endoplasmic Reticulum/pathology ; Humans ; Mice, Transgenic ; Molecular Weight ; Nerve Degeneration/metabolism ; Nerve Degeneration/pathology ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology ; Neurons/pathology ; Primary Cell Culture ; Protein Aggregation, Pathological/pathology ; alpha-Synuclein/chemistry ; alpha-Synuclein/genetics
مستخلص: α-synuclein (αS) is a small protein that self-aggregates into α-helical oligomer species and subsequently into larger insoluble amyloid fibrils that accumulate in intraneuronal inclusions during the development of Parkinson's disease. Toxicity of αS oligomers and fibrils has been long debated and more recent data are suggesting that both species can induce neurodegeneration. However while most of these data are based on differences in structure between oligomer and aggregates, often preassembled in vitro, the in vivo situation might be more complex and subcellular locations where αS species accumulate, rather than their conformation, might contribute to enhanced toxicity. In line with this observation, we have shown that αS oligomers and aggregates are associated with the endoplasmic reticulum/microsomes (ER/M) membrane in vivo and how accumulation of soluble αS oligomers at the ER/M level precedes neuronal degeneration in a mouse model of α-synucleinopathies. In this paper we took a further step, investigating the biochemical and functional features of αS species associated with the ER/M membrane. We found that by comparison with non-microsomal associated αS (P10), the ER/M-associated αS pool is a unique population of oligomers and aggregates with specific biochemical traits such as increased aggregation, N- and C-terminal truncations and phosphorylation at serine 129. Moreover, when administered to murine primary neurons, ER/M-associated αS species isolated from diseased A53T human αS transgenic mice induced neuronal changes in a time- and dose-dependent manner. In fact the addition of small amounts of ER/M-associated αS species from diseased mice to primary cultures induced the formation of beads-like structures or strings of fibrous αS aggregates along the neurites, occasionally covering the entire process or localizing at the soma level. By comparison treatment with P10 fractions from the same diseased mice resulted in the formation of scarce and small puncta only when administered at high amount. Moreover, increasing the amount of P100/M fractions obtained from diseased and, more surprisingly, from presymptomatic mice induced a significant level of neuronal death that was prevented when neurons were treated with ER/M fractions immunodepleted of αS high molecular weight (HMW) species. These data provide the first evidence of the existence of two different populations of αS HMW species in vivo, putting the spotlight on the association to ER/M membrane as a necessary step for the acquisition of αS toxic features.
(Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
References: J Biol Chem. 2002 Jan 4;277(1):671-8. (PMID: 11679584)
Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8968-73. (PMID: 12084935)
Neurotoxicology. 2002 Oct;23(4-5):527-36. (PMID: 12428725)
J Biol Chem. 2003 Apr 25;278(17):15313-8. (PMID: 12586824)
Annu Rev Neurosci. 2003;26:267-98. (PMID: 12704221)
Science. 2003 Oct 31;302(5646):841. (PMID: 14593171)
Ann Neurol. 2004 Feb;55(2):164-73. (PMID: 14755719)
J Neurosci. 2004 Aug 18;24(33):7400-9. (PMID: 15317865)
Lancet. 2004 Sep 25-Oct 1;364(9440):1167-9. (PMID: 15451224)
Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):2162-7. (PMID: 15684072)
Biochemistry. 2005 Jun 14;44(23):8251-9. (PMID: 15938614)
J Neurosci. 2005 Jun 22;25(25):6016-24. (PMID: 15976091)
J Neurosci. 2006 Jan 4;26(1):41-50. (PMID: 16399671)
Science. 2006 Jul 21;313(5785):324-8. (PMID: 16794039)
J Neurosci. 2007 Feb 7;27(6):1405-10. (PMID: 17287515)
Mol Cell Biochem. 2009 Jun;326(1-2):55-66. (PMID: 19116775)
Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20051-6. (PMID: 19892735)
Mol Biol Cell. 2010 Jun 1;21(11):1850-63. (PMID: 20392839)
Prog Brain Res. 2010;183:115-45. (PMID: 20696318)
Science. 2010 Sep 24;329(5999):1663-7. (PMID: 20798282)
Annu Rev Pathol. 2011;6:193-222. (PMID: 21034221)
Nature. 2011 Aug 14;477(7362):107-10. (PMID: 21841800)
Neuron. 2011 Oct 6;72(1):57-71. (PMID: 21982369)
Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17797-802. (PMID: 22006323)
J Biol Chem. 2012 May 4;287(19):15345-64. (PMID: 22315227)
J Neurosci. 2012 Mar 7;32(10):3301-5. (PMID: 22399752)
J Neurosci. 2012 Mar 7;32(10):3306-20. (PMID: 22399753)
Cell. 2012 May 25;149(5):1048-59. (PMID: 22632969)
Nat Protoc. 2012 Sep;7(9):1741-54. (PMID: 22936216)
Science. 2012 Nov 16;338(6109):949-53. (PMID: 23161999)
Nat Rev Neurol. 2013 Jan;9(1):13-24. (PMID: 23183883)
Mov Disord. 2013 Jun;28(6):811-3. (PMID: 23457019)
Ann Neurol. 2013 Apr;73(4):459-71. (PMID: 23526723)
Trends Mol Med. 2013 Jun;19(6):368-77. (PMID: 23648364)
Nature. 2013 Jun 13;498(7453):E4-6; discussion E6-7. (PMID: 23765500)
Neuron. 2013 Sep 18;79(6):1044-66. (PMID: 24050397)
Nat Protoc. 2014 Sep;9(9):2135-46. (PMID: 25122523)
Proc Natl Acad Sci U S A. 2014 Oct 7;111(40):E4274-83. (PMID: 25246573)
Biomolecules. 2015 Mar 25;5(2):282-305. (PMID: 25816357)
Nature. 2015 Jun 18;522(7556):340-4. (PMID: 26061766)
Nat Commun. 2015 Jun 16;6:7314. (PMID: 26076669)
J Parkinsons Dis. 2015;5(4):699-713. (PMID: 26407041)
Nature. 2016 Feb 4;530(7588):45-50. (PMID: 26808899)
J Neurochem. 2016 Oct;139(2):162-180. (PMID: 27529376)
J Biol Chem. 2017 Aug 11;292(32):13482-13497. (PMID: 28611062)
J Neurosci. 1988 Aug;8(8):2804-15. (PMID: 3411354)
Neuron. 1995 Feb;14(2):467-75. (PMID: 7857654)
Biochemistry. 1996 Oct 29;35(43):13709-15. (PMID: 8901511)
Science. 1997 Jun 27;276(5321):2045-7. (PMID: 9197268)
Brain Res. 1997 Nov 14;775(1-2):24-9. (PMID: 9439824)
Nat Genet. 1998 Feb;18(2):106-8. (PMID: 9462735)
Nat Med. 1998 Nov;4(11):1318-20. (PMID: 9809558)
معلومات مُعتمدة: R01 NS086074 United States NS NINDS NIH HHS; R01 NS092093 United States NS NINDS NIH HHS
فهرسة مساهمة: Keywords: Aggregates; Endoplasmic reticulum; Microsomes; Neurodegeneration; Oligomers; Parkinson's disease; α-Synuclein
المشرفين على المادة: 0 (SNCA protein, human)
0 (alpha-Synuclein)
تواريخ الأحداث: Date Created: 20171217 Date Completed: 20190617 Latest Revision: 20220331
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6705388
DOI: 10.1016/j.nbd.2017.12.004
PMID: 29246724
قاعدة البيانات: MEDLINE
الوصف
تدمد:1095-953X
DOI:10.1016/j.nbd.2017.12.004