Home Cell Biology Generation of Alpha-Synuclein Preformed Fibrils from Monomers and Use In Vivo
Cell Biology JoVE (Open Access) Citable · DOI

Generation of Alpha-Synuclein Preformed Fibrils from Monomers and Use In Vivo

DOI: 10.3791/59758-v
What you'll learn
  • Generate alpha-synuclein preformed fibrils from monomeric protein
  • Perform quality control analysis of fibril preparations
  • Prepare stereotactic injection needles for in vivo delivery
  • Administer preformed fibrils to animal models
Protocol

Biopharma Insights The goal of this article is to outline the steps required for the generation of fibrils from monomeric alpha-synuclein, subsequent quality control, and use of the preformed fibrils in vivo.

Difficulty
advanced
Total time
~3-5 days (fibril generation and quality control); ~2 hours per animal (stereotactic surgery)
Model organism
Mouse (unspecified strain)
Biosafety
BSL-1

Steps

1
Form alpha-synuclein preformed fibrils from monomers

Incubate monomeric alpha-synuclein under conditions that promote self-assembly into fibrillar structures. Monitor fibril formation over time.

▶ 01:13
2
Sonicate alpha-synuclein preformed fibrils

Fragment the generated fibrils via sonication to produce smaller, uniform fibril seeds suitable for injection. Confirm size reduction.

▶ 02:20
3
Prepare custom glass needle syringes for injection

Pull and polish glass capillaries to create fine-gauge needles compatible with stereotactic apparatus for precise brain injection.

▶ 04:37
4
Analyze generated alpha-synuclein preformed fibrils

Characterize fibril morphology, size distribution, and biochemical properties using electron microscopy and complementary biophysical methods.

▶ 07:18
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