Induction of CNS α-synuclein pathology by fibrillar and non-amyloidogenic recombinant α-synuclein
Authors: Yong Ran
Amanda N Sacino
Benoit I Giasson
Alex B McKinney
Todd E Golde
Yona Levites
Michael A Thomas
Mieu Brooks
Nicholas H McGarvey
Journal: Acta Neuropathologica Communications (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: α-Synuclein; Lewy bodies; Parkinson's disease; aggregation; synucleinopathies
Affiliations: Center for Translational Research in Neurodegenerative Disease, Department of Neuroscience, BMS Building J-483, University of Florida College of Medicine, 1275 Center Drive, PO Box 100159, Gainesville, FL 32610, USA. .

Abstract:  Background: α-Synuclein (αS) is the major component of several types of brain inclusions including Lewy bodies, a hallmark of Parkinson's disease. Aberrant aggregation of αS also is associated with cellular demise in multiple neurologic disorders collectively referred to as synucleinopathies. Recent studies demonstrate the induction of αS pathology by a single intracerebral injection of exogenous amyloidogenic αS in adult non-transgenic and transgenic mice expressing human αS. To further investigate the mechanism of pathology induction and evaluate an experimental paradigm with potential for higher throughput, we performed similar studies in neonatal mice injected with αS. Results: In non-transgenic mice, we observed limited induction of neuronal αS inclusions predominantly 8 months after brain injection of aggregated, amyloidogenic human αS. More robust inclusion pathology was induced in transgenic mice expressing wild-type human αS (line M20), and inclusion pathology was observed at earlier time points. Injection of a non-amyloidogenic (Δ71-82) deletion protein of αS was also able to induce similar pathology in a subset of M20 transgenic mice. M20 transgenic mice injected with amyloidogenic or non-amyloidogenic αS demonstrated a delayed and robust induction of brain neuroinflammation that occurs in mice with or without αS pathological inclusions implicating this mechanism in aggregate formation. Conclusions: The finding that a non-amyloidogenic Δ71-82 αS can induce pathology calls into question the simple interpretation that exogenous αS catalyzes aggregation and spread of intracellular αS pathology solely through a nucleation dependent conformational templating mechanism. These results indicate that several mechanisms may act synergistically or independently to promote the spread of αS pathology. 

Retracted: No

PubPeer comments:
 Plagiarising a [comment by Elisabeth Bik] : This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels. Despite these similarities, these papers are authored by researchers from different departments and institutes, with almost no overlap in authors. The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing A more detailed description of this set of papers, suspected to all be generated by a common source, a paper mill , can be found here: - https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers (January 2020) - https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill (February 2020) The same paper mill has been described in these papers: - Jana Christopher - Systematic fabrication of scientific images revealed - FEBS Letters (2018) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13201 - Jennifer A Byrne and Jana Christopher - Digital magic, or the dark arts of the 21st centuryu2014how can journals and peer reviewers detect manuscripts and publications from paper mills? - FEBS Letters (2020) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13747 ![file] , 
 Retracted [24 August 2021] . H t [RetractionWatch] . ----------------------------------- At the request of the Journal Editor the following article has been retracted. Wang P, Liu G, Xu W, Liu H, Bu Q, Sun D. Long Noncoding RNA H19 Inhibits Cell Viability, Migration, and Invasion Via Downregulation of IRS-1 in Thyroid Cancer Cells. Technology in Cancer Research Treatment, DOI:10.1177 1533034617733904 Significant similarities between this paper and a number of other papers have been identified, as well as indication of image and data manipulation suggestive of the use of a u201cpaper millu201d. These papers share common structures and wording yet do not share any common authors. The authors did not provide a sufficient response or evidence to refute these claims. As a result, the scientific accuracy of this paper is not reliable. Adhering to the international guidelines established by the Committee on Publication Ethics, the Journal has determined these are grounds for retraction. ,