Related Experiment Video
Updated: Jul 10, 2026
09:00
Biochemical Purification and Proteomic Characterization of Amyloid Fibril Cores from the Brain
Published on: April 28, 2022
Phase separation and protein aggregation in neurodegenerative diseases
Hortense de La Seiglière1, Ænora Letourneur1, François Ichas2
1SynTeam, Institut des maladies neurodégénératives, CNRS UMR5293, Univ. Bordeaux, France.
Biophysical Chemistry
|July 8, 2026
Summary
Liquid-liquid phase separation (LLPS) of proteins like Tau and alpha-synuclein is implicated in neurodegenerative diseases. Aberrant LLPS can drive amyloid aggregation, contributing to diseases such as Alzheimer's and Parkinson's.
Area of Science:
- Biochemistry
- Cell Biology
- Neuroscience
Background:
- Neurodegenerative diseases involve amyloid protein aggregation.
- Intrinsically disordered proteins (IDPs) are implicated in these diseases.
- IDPs are capable of liquid-liquid phase separation (LLPS), forming dynamic membraneless organelles.
Purpose of the Study:
- To review the role of LLPS in regulating amyloid aggregation in neurodegenerative diseases.
- To examine how mutations, PTMs, and environmental factors affect LLPS of key proteins (Tau, TDP-43, FUS, α-synuclein).
- To explore the interplay of these proteins and LLPS in disease co-pathologies and progression.
Main Methods:
- Literature review of studies on LLPS and neurodegenerative diseases.
- Analysis of factors modulating LLPS of Tau, TDP-43, FUS, and α-synuclein.
- Examination of the connection between LLPS, condensate maturation, and co-pathologies.
Main Results:
- LLPS can either limit or promote amyloid fibrillation depending on cellular conditions.
- Mutations, PTMs, and environmental factors significantly influence LLPS of disease-associated proteins.
- Aberrant LLPS and condensate maturation may contribute to the emergence of co-pathologies.
Conclusions:
- LLPS is a critical process in the pathogenesis of neurodegenerative diseases.
- Modulating LLPS dynamics presents a promising therapeutic avenue.
- Understanding LLPS mechanisms is key to developing effective treatments for Alzheimer's, Parkinson's, ALS, and FTD.
Related Concept Videos
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:24Parkinson Disease ll: Pathophysiology
Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
01:23Alzheimer Disease ll: Pathophysiology
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...