Current safety recommendations for handling mouse and human αsynuclein pre-formed fibrils
Neurobiology of Disease. 2025-03-01; 206: 106820
DOI: 10.1016/j.nbd.2025.106820
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Fielding L(1), Menard MA(2), Roth J(3), Iuliano M(4), Dehay B(5), Aguilar-Calvo P(6), Volpicelli-Daley LA(7).
Author information:
(1)Center for Neurodegeneration and Experimental Therapeutics, Department of
Neurology, 1719 6th Avenue South, University of Alabama at Birmingham,
Birmingham, AL 35294, USA. Electronic address: .
(2)Center for Neurodegeneration and Experimental Therapeutics, Department of
Neurology, 1719 6th Avenue South, University of Alabama at Birmingham,
Birmingham, AL 35294, USA. Electronic address: .
(3)Environmental Health and Safety, 933 19(th) Street South, University of
Alabama at Birmingham, Birmingham, AL 35205, USA. Electronic address:
.
(4)Department of Neurology, Yale School of Medicine, New Haven, CT 06511 and
Department of Neuroscience, Tufts University School of Medicine, Boston, MA
02111, USA; Aligning Science Across Parkinson’s (ASA) Collaborative Research
Network, Chevy Chase, MD 20815, USA. Electronic address: .
(5)University Bordeaux, CNRS, IMN, Bordeaux, France. Electronic address:
.
(6)Center for Neurodegeneration and Experimental Therapeutics, Department of
Neurology, 1719 6th Avenue South, University of Alabama at Birmingham,
Birmingham, AL 35294, USA. Electronic address: .
(7)Center for Neurodegeneration and Experimental Therapeutics, Department of
Neurology, 1719 6th Avenue South, University of Alabama at Birmingham,
Birmingham, AL 35294, USA; Aligning Science Across Parkinson’s (ASA)
Collaborative Research Network, Chevy Chase, MD 20815, USA. Electronic address:
.
α-Synuclein (α-syn) can form amyloid fibrils. Lewy bodies and Lewy neurites
containing aggregated α-syn are pathological markers of Parkinson’s Disease and
Dementia with Lewy Bodies. To better understand the role of pathological α-syn
in disease, many labs use α-syn preformed fibrils (PFFs). Neurons take up the
PFFs, which act as seeds to corrupt endogenously expressed α-syn, inducing it to
form aggregates very similar to those found in diseased brains. The PFFs are
typically generated using recombinant mouse or human α-syn. α-Syn fibrils can
also be extracted or amplified from brain tissue extracts, cerebrospinal fluid,
or skin biopsies from patients with known synucleinopathy. The PFFs are then
added to cell culture, or injected into rodents or primates to induce pathology.
Because PFFs can corrupt endogenous α-syn, researchers should adhere to strict
safety protocols when handling PFFs to minimize potential exposures. Our group
consulted with biosafety professionals at the University of Alabama at
Birmingham (UAB) to identify potential risks related to working with α-syn PFFs
and offer containment controls to mitigate those risks. Potential exposures
include pipetting, opening tubes, and sonication of the PFFs to generate
fragments, all of which could potentially generate aerosols. Here, we outline
best practices for the safe conduct of research with α-syn fibrils, including
personal protective equipment and decontamination procedures. We highlight steps
in which extra precautions should be taken and how to minimize exposure and
potential risk associated with use of PFFs in scientific research.
Copyright © 2024. Published by Elsevier Inc.
DOI: 10.1016/j.nbd.2025.106820
PMID: 39889858