No abstract

αB-Crystallin, which has homology with the small heat shock proteins, is the basic subunit of α-crystallin, a major component of the vertebrate eye lens. These crystallins have for a long time been thought to be absolutely lens specific. However, about a decade ago αB-crystallin has been detected extralenticularly in many tissues among which the central nervous system. Under pathological conditions the expression level of αB-crystallin frequently increases. For this reason it is considered to be a useful marker in a variety of neurodegenerative diseases. In this mini-review, a number of typical neurodegenerative disorders is dealt with in which αB-crystallin may play a role.

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Homozygous mice transgenic for alphaA-crystallin, one of the structural eye lens proteins, developed hindlimb paralysis after 8 weeks of age. To unravel the pathogenesis of this unexpected finding and the possible role of alphaA-crystallin in this pathological process, mice were subjected to a histopathological and immunohistochemical investigation. Immunohistochemistry showed large deposits of alphaA-crystallin in the astrocytes of the spinal cord, and in the Schwann cells of dorsal roots and sciatic nerves. Additionally, microscopy showed dystrophic axons in the spinal cord and digestion chambers as a sign of ongoing demyelination in dorsal roots and sciatic nerves. Apart from a few areas with slight alphaA-crystallin-immunopositive structures, the brain was normal. Because the alphaA-crystallin protein expression appeared in specific cells of the nervous system (astrocytes and Schwann cells), the most plausible explanation for the paralysis is a disturbance of cell function caused by the excessive intracytoplasmic accumulation of the alphaA-crystallin protein. This is followed by a sequence of secondary changes (demyelination, axonal dystrophy) and finally arthrosis. In conclusion, alphaA-crystallin transgenic mice develop a peripheral and central neuropathy primarily affecting spinal cord areas at the dorsal side, dorsal root and sciatic nerve.

K KA-Crystallin, a small heat shock protein with chaperone-like activity, forms dynamic multimeric complexes. Recently we described the spontaneous generation of a mutant protein (super K KA-crystallin) by exon duplication arisen via exon shuffling confirming a classic hypothesis by Gilbert [Nature 271 (1978) 501]. Comparison of super K KA-crystallin, which is viable in a mouse skeletal muscle cell line, with normal K KAcrystallin shows that it has diminished thermostability, increased exposure of hydrophobic patches, a larger complex size and lost its chaperone activity. However, super K KA-crystallin subunits exchange as readily between complexes as does normal K KAcrystallin. These data indicate that chaperone-like activity may vanish independent of subunit hydrophobicity and exchangeability. ß