HUNTINGTONS-DISEASE - FROM MORPHOLOGY TO MOLECULAR NEUROPATHOLOGY

The conventional neuropathologic approach to Huntington's disease culm inated in the classification developed by Vonsattel. Molecular biology studies of human and experimental material have provided new insight into the lesions of this disease characterized by an abnormally large number of CAG triplet repeats in a mutant gene, a mechanism also known to occur in ten or so other ''molecular'', neurologic diseases. The p rotein encoded by the HD locus (huntingtin) is associated with another protein (HAP-I), which enhances its toxic potential; huntingtin inter acts with the enzyme GADPH, and its cleavage by apopain may lead to in appropriate apoptosis. Interactions between huntingtin, HAP-1, GADPH, and apopain may be modulated by the presence of polyglutamines.