Co-chaperoning by amyloid-forming proteins: cystatins vs. crystallins

Cystatins and crystallins are both neuroprotective proteins. Except for their function as cysteine cathepsins inhibitors, cystatins are A beta binding proteins and presumably protect neurons from intracellular A beta and extracellular A beta plaques. Pathological mutations of cystatin C cause amyloid angiopathy. Crystallins, known as small heat shock proteins, bind not only A beta peptide but also other crystallins in the eye lens and prevent their aggregation. Mutations in crystallins cause cataracts and myopathies. Cross-interactions between amyloidogenic proteins, intrinsically disordered and folded proteins, can also occur. I term the nonspecific binding between amyloidogenic proteins and peptides "co-chaperoning." A wide range of other A beta binding proteins exist, such as catalase, lysozyme, beta-lactoglobulin and some other abundant proteins found in plasma.