Protein misfolding

Protein misfolding is the adoption of a structure that differs from a protein’s functional native state. Misfolded proteins can lose function, aggregate, or be repaired or degraded by cellular quality-control systems.

Protein folding: The process by which a protein adopts its functional three-dimensional structure. Misfolding is a failure or diversion of this structural maturation process.
Alzheimer's disease: A progressive neurodegenerative disease associated with cognitive decline and characteristic brain protein pathology. Amyloid-beta and tau misfolding and aggregation are central features of its pathology.
Protein structure: The hierarchy of amino-acid sequence and three-dimensional arrangements that determines a protein’s properties. Misfolding means a departure from the functional structure within this hierarchy.
Protein-folding problem: The challenge of predicting a protein’s three-dimensional structure from its amino-acid sequence and conditions. Understanding misfolding depends on explaining which structures a sequence can adopt and why.
Molecular chaperone: A protein that assists other proteins in folding or prevents their inappropriate aggregation. Chaperones can rescue folding intermediates before they become persistently misfolded.
Parkinson's disease: A progressive neurological disorder marked by movement symptoms and degeneration of dopamine-producing neurons. Misfolded alpha-synuclein aggregates form Lewy bodies in affected neurons.
Native state: The biologically functional, folded state or ensemble adopted by a protein under particular conditions. It provides the reference state against which misfolding is defined.
Amyloid hypothesis: The proposal that amyloid-beta accumulation initiates a cascade leading to Alzheimer's disease. It raises the unresolved question of whether amyloid is a cause, driver, or marker of disease.
Unfolded protein response: A cellular stress response that adjusts protein production and disposal when unfolded proteins accumulate in the endoplasmic reticulum. It responds when misfolded proteins overwhelm quality control in the endoplasmic reticulum.
Prion disease: A group of fatal disorders caused by misfolded prion proteins that can induce misfolding of normal prion protein. It demonstrates how a misfolded protein can propagate its structure between molecules.

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