Studies of protein aggregation in A53T α-synuclein transgenic, Tg2576 transgenic, and P246L presenilin-1 knock-in cross bred mice

NEUROSCIENCE LETTERS

卷:507

Article

Giasson, Benoit I.¹ 

[1] Univ Penn, Dept Pharmacol, Sch Med, Philadelphia, PA 19104 USA

关键词: Aggregation;    Amyloid;    Pathology;    Parkinson disease;    alpha-Synuclein;    Transgenic;   

DOI  :  10.1016/j.neulet.2011.12.005

来源: Elsevier

【 摘 要 】

Synucleinopathies are a group of neurodegenerative disorders, including Parkinson disease, associated with neuronal amyloid inclusions comprised of the presynaptic protein alpha-synuclein (alpha-syn); however the biological events that initiate and lead to the formation of these inclusions are still poorly understood. There is mounting evidence that intracellular alpha-syn aggregation may proceed via a seeding mechanism and could spread between neurons through a prion-like mechanism that may involve other amyloidogenic proteins. Several lines of evidence suggest that A beta peptides and/or extracellular A beta deposits may directly or indirectly promote intracellular alpha-syn aggregation. To assess the effects of A beta peptides and extracellular A beta deposits on alpha-syn aggregate formation, transgenic mice (line M83) expressing A53T human alpha-syn that are sensitive to developing alpha-syn pathological inclusions were cross bred to Tg2576 transgenic mice that generated elevated levels of A beta peptides and develop abundant A beta plaques. In addition these mice were bred to mice with the P264L presenilin-1 knock-in mutation that further promotes A beta plaque formation. These mice demonstrated the expected formation of A beta plaques; however despite the accumulation of hyperphosphorylated alpha-syn dystrophic neurites within or surrounding A beta plaques, no additional alpha-syn pathologies were observed. These studies show that A beta amyloid deposits can cause the local aggregation of alpha-syn, but these did not lead to more extensive alpha-syn pathology. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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