- The next treatment for neurodegenerative diseases?
Research in animal models has suggested that the commonly used Congo red fluorophore can disrupt the formation of amyloids, the misfolded proteins believed to cause afflictions such as Alzheimer’s and Parkinson’s disease. Researchers at Lund University in Sweden have reviewed the evidence for Congo red’s ameliorative effects on neurodegenerative diseases.
The authors cite examples pertaining to several neurodegenerative diseases. For example, in cultured rat hippocampal neurons and in flies engineered to produce β-amyloid, a misfolded protein that may be responsible for Alzheimer’s disease, the fluorophore prevented the amyloid’s aggregation and prolonged the flies’ survival. Several studies have shown that Congo red can disrupt the uptake of prions, the misfolded proteins behind mad cow disease, especially at early stages of prion infection. Additionally, the fluorophore obstructs the accumulation of α-synuclein — the amyloid found in patients with Parkinson’s disease — and blocks the formation of ion channels by the amyloid. Some studies suggest that ion channel formation is important in amyloid pathogenesis.
Congo red has restored the phenotype of transgenic mice and flies expressing mutant huntingtin, the amyloid that causes Huntington’s disease. For example, transgenic mice of the R6/2 strain exhibit abnormal motor function, muscle atrophy, diabetes, weight loss and huntingtin protein aggregation in the brain. Administration of Congo red alleviates these symptoms. Likewise, flies that express huntingtin have shortened lifespans and have misfolded proteins in their primitive neural system. The fluorophore enables them to live longer and reduces the amount of amyloid in their neural system.
Congo red can cause other effects. It mitigates several intracellular changes such as an altered redox environment and redistributed nuclear enzymes caused by neurodegenerative diseases. It can interfere with glycosaminoglycans, factors thought to be part of the amyloid pathogenesis pathway. In addition to its role in neurodegenerative diseases, the fluorophore can kill viruses and affect immune processes such as inflammation.
Although much evidence suggests that Congo red prevents the development of amyloids, two disadvantages may prevent it from becoming an accepted treatment, at least in its current form. It cannot easily penetrate the blood-brain barrier, and it can cause cancer. However, analogs of Congo red might have the amyloid-fighting properties of the fluorophore without the negative consequences. (Brain Research Reviews, January 2007, pp. 135-160).
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