Morphogenesis of Lewy bodies: dissimilar incorporation of alpha-synuclein, ubiquitin, and p62.

作者: Erkki Kuusisto , Laura Parkkinen , Irina Alafuzoff

DOI: 10.1093/JNEN/62.12.1241

关键词: Lewy bodyCytoplasmAlpha-synucleinCell biologyBiologyH&E stainCytoplasmic inclusionPathologyStainingAggresomeSequestosome 1

摘要: The formation of Lewy bodies (LBs) and their relationship to other types nigral inclusions associated with Parkinson disease (PD), such as pale (PBs), remain poorly understood. Known constituents LBs include alpha-synuclein (alphaS) ubiquitin (Ub), providing windows morphogenesis. Additionally, p62/sequestosome 1 has been identified a common component neuropathological hepatocytic inclusions. To study the PD-associated inclusions, we analyzed substantia nigra cases abundant PBs in hematoxylin eosin (H&E) stain, using immunohistochemistry for alphaS, Ub, p62. We found morphologically diverse alphaS-immunoreactive deposits within neuronal perikarya neurites. Perikaryal extended from punctate cytoplasmic staining variform compact (i.e. PB-type LB-type) Using H&E, only small subset could be unambiguously identified. Labeling p62 was highly similar alphaS perikaryal whereas no or intraneuritic were detected. Ubiquitin antibodies labeled both data suggest that pathological is first evident material that, via coalescence incorporation yields structures which LB-type form compaction-like manner. results also point at dissimilarities vs

参考文章(48)
Laura Parkkinen, Hilkka Soininen, Irina Alafuzoff, Regional distribution of alpha-synuclein pathology in unimpaired aging and Alzheimer disease. Journal of Neuropathology and Experimental Neurology. ,vol. 62, pp. 363- 367 ,(2003) , 10.1093/JNEN/62.4.363
Eva Braak, Daniele Sandmann-Keil, Udo Rüb, Wei Ping Gai, Rob A. I. de Vos, Ernst N. H. Jansen Steur, Kimihito Arai, Heiko Braak, alpha-synuclein immunopositive Parkinson's disease-related inclusion bodies in lower brain stem nuclei. Acta Neuropathologica. ,vol. 101, pp. 195- 201 ,(2001) , 10.1007/S004010000247
Hideo Fujiwara, Masato Hasegawa, Naoshi Dohmae, Akiko Kawashima, Eliezer Masliah, Matthew S. Goldberg, Jie Shen, Koji Takio, Takeshi Iwatsubo, |[alpha]|-Synuclein is phosphorylated in synucleinopathy lesions Nature Cell Biology. ,vol. 4, pp. 160- 164 ,(2002) , 10.1038/NCB748
G. G. Fillenbaum, A. Heyman, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neurology. ,vol. 44, pp. 228- 228 ,(2002) , 10.1002/0470846410.CH42(III)
Minami Baba, S. Nakajo, Pang-Hsien Tu, T. Tomita, Kazuyasu Nakaya, VM Lee, John Q Trojanowski, T. Iwatsubo, Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies. American Journal of Pathology. ,vol. 152, pp. 879- 884 ,(1998)
Elisabeth Leroy, Rebecca Boyer, Georg Auburger, Barbara Leube, Gudrun Ulm, Eva Mezey, Gyongyi Harta, Michael J. Brownstein, Sobhanadditya Jonnalagada, Tanya Chernova, Anindya Dehejia, Christian Lavedan, Thomas Gasser, Peter J. Steinbach, Keith D. Wilkinson, Mihael H. Polymeropoulos, The ubiquitin pathway in Parkinson's disease Nature. ,vol. 395, pp. 451- 452 ,(1998) , 10.1038/26652
Tohru Kitada, Shuichi Asakawa, Nobutaka Hattori, Hiroto Matsumine, Yasuhiro Yamamura, Shinsei Minoshima, Masayuki Yokochi, Yoshikuni Mizuno, Nobuyoshi Shimizu, Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism Nature. ,vol. 392, pp. 605- 608 ,(1998) , 10.1038/33416
Jianping Gong, Jia Xu, Magdalena Bezanilla, Rika van Huizen, Rachel Derin, Min Li, Differential Stimulation of PKC Phosphorylation of Potassium Channels by ZIP1 and ZIP2 Science. ,vol. 285, pp. 1565- 1569 ,(1999) , 10.1126/SCIENCE.285.5433.1565
Ross Jakes, R.Anthony Crowther, Virginia M.-Y. Lee, John Q. Trojanowski, Takeshi Iwatsubo, Michel Goedert, Epitope mapping of LB509, a monoclonal antibody directed against human α-synuclein Neuroscience Letters. ,vol. 269, pp. 13- 16 ,(1999) , 10.1016/S0304-3940(99)00411-5
Eizo Iseki, Wami Marui, Haruhiko Akiyama, Kenji Uéda, Kenji Kosaka, Degeneration process of Lewy bodies in the brains of patients with dementia with Lewy bodies using α-synuclein-immunohistochemistry Neuroscience Letters. ,vol. 286, pp. 69- 73 ,(2000) , 10.1016/S0304-3940(00)01090-9