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Weizmann researchers find evidence that links molecular mechanism to Huntington's Disease

Weizmann researchers have found evidence that an enzyme called transglutaminase (TGase) may be the "smoking gun" behind the deadly disease Huntington's disease (HD). Their study is reported in the June 22 issue of the Proceedings of the National Academy of Sciences.

TGase occurs naturally throughout the body, and is catalyst for processes associated with healing, such as skin formation and wound healing. But a 1993 study by Prof. Howard Green (now of the Department of Cell Biology, Harvard Medical School, Boston) suggested that because of their polymerizing properties, they might also act as a catalyst for aggregating a protein associated with HD called Huntingtin (htt). Prof. Lawrence Steinman (then of the Weizmann Institute's Department of Immunology, now of Stanford University's Department of Neurological Science), together with Weizmann graduate student, Marcela Karpuj and a team of researchers in the United States, have now provided clear evidence of elevated TGase activity in the postmortem brains of HD patients.

Patients who suffer from HD have aggregations "visible clumps"of htt in their brains, but not in other tissues. This makes aggregated htt a good pathological indicator for the disease. Steinman, Karpuj, and the other members of the team decided to look for a correlation between clumps of htt and TGase among patients with HD. They found elevated TGase activity in the cortex, the cerebellum, and the brain nuclei--all areas in the brain where htt gets concentrated into nuclear inclusions. Correspondingly, they found reduced TGase activity in lymphoblastoid cells--areas where htt does not aggregate. TGase, therefore, appears to be the "smoking gun" that leads to the formation of nuclear inclusions (htt aggregations) in HD patients.

Their research is unique, because for the first time, researchers were able to report on TGase activity in the brains of HD patients rather than in guinea pigs or rats. They compared five postmortem brains of HD
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Contact: Ellen Shnidman
ellens@acwis.org
212-779-2500
American Committee for the Weizmann Institute of Science
21-Jun-1999


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