Congo red and protein aggregation in neurodegenerative diseases

• Published in: Brain Research Reviews Vol. 53; no. 1; pp. 135 - 160
• Main Authors: Frid, Petrea, Anisimov, Sergey V, Popovic, Natalija
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2007
• Subjects: Alzheimer's disease; Amyloid; Amyloid beta-Peptides; Amyloid beta-Peptides - antagonists & inhibitors; Amyloid beta-Peptides - metabolism; Amyloid beta-Peptides - toxicity; Animals; Basic Medicine; Coloring Agents; Coloring Agents - chemistry; Coloring Agents - pharmacology; Coloring Agents - therapeutic use; Complement; Congo Red; Congo Red - chemistry; Congo Red - pharmacology; Congo Red - therapeutic use; Glycosaminoglycan; Humans; Huntington's disease; Imaging probe; Inclusion; Inclusion Bodies; Inclusion Bodies - drug effects; Inclusion Bodies - metabolism; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Microglia; Neurodegenerative Diseases; Neurodegenerative Diseases - drug therapy; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - physiopathology; Neurology; Neuroprotective Agents; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurosciences; Neurovetenskaper; Parkinson's disease; Plaque, Amyloid; Plaque, Amyloid - drug effects; Plaque, Amyloid - metabolism; Prion disease; Protein configuration; Protein Folding; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review; Staining and Labeling; Staining and Labeling - methods; Staining and Labeling - trends; Prion disease; Congo red; Inclusion; Parkinson's disease; Glycosaminoglycan; Amyloid; Complement; Huntington's disease; Imaging probe; Protein configuration; Alzheimer's disease; Microglia
• ISSN: 0165-0173; 1872-6321; 1872-6321
• DOI: 10.1016/j.brainresrev.2006.08.001

Abstract Congo red is a commonly used histological dye for amyloid detection. The specificity of this staining results from Congo red's affinity for binding to fibril proteins enriched in β-sheet conformation. Unexpectedly, recent investigations indicate that the dye also possesses the capacity to interfere with processes of protein misfolding and aggregation, stabilizing native protein monomers or partially folded intermediates, while reducing concentration of more toxic protein oligomers. Inhibitory effects of Congo red upon amyloid toxicity may also range from blockade of channel formation and interference with glycosaminoglycans binding or immune functions, to the modulation of gene expression. Particularly, Congo red exhibits ameliorative effect in models of neurodegenerative disorders, such as Alzheimer's, Parkinson's, Huntington's and prion diseases. Another interesting application of Congo red analogues is the development of imaging probes. Based on their small molecular size and penetrability through blood–brain barrier, Congo red congeners can be used for both antemortem and in vivo visualization and quantification of brain amyloids. Therefore, understanding mechanisms involved in dye-amyloidal fibril binding and inhibition of aggregation will provide instructive guides for the design of future compounds, potentially useful for monitoring and treating neurodegenerative diseases.