Neuroscience

Disease

Protein folding

Amyloid (mycology)

Biology

Protein aggregation

Oligomer

Philosophy

Neurodegeneration

Medicine

Biochemistry

Computational biology

Drug discovery

Mechanism (biology)

Organic chemistry

Bioinformatics

Confusion

Epistemology

Psychoanalysis

Psychology

Chemistry

Pathology

Nature Reviews Chemistry

Protein misfolding and aggregation are characteristic of a wide range of neurodegenerative disorders, including Alzheimer and Parkinson diseases. A hallmark of these diseases is the aggregation of otherwise soluble and functional proteins into amyloid aggregates. Although for many decades such amyloid deposits have been thought to be responsible for disease progression, it is now increasingly recognized that the misfolded protein oligomers formed during aggregation are, instead, the main agents causing pathological processes. These oligomers are transient and heterogeneous, which makes it difficult to detect and quantify them, generating confusion about their exact role in disease. The lack of suitable methods to address these challenges has hampered efforts to investigate the molecular mechanisms of oligomer toxicity and to develop oligomer-based diagnostic and therapeutic tools to combat protein misfolding diseases. In this Review, we describe methods to quantify misfolded protein oligomers, with particular...

Quantifying misfolded protein oligomers as drug targets and biomarkers in Alzheimer and Parkinson diseases