The genetic disease, Alpha 1, caused by a defective AAT gene, is more prevalent than HD. HSP27 is studied because it protects eyes. AAT is a treatable genetic disorder. Drugs that treat AAT are candidates for the treatment of HD. HSP27 is thought to be neuroprotective and deliverable by virus.

The hope of stem cell implants to cure HD dims because of the finding that HD also acts outside the brain. Two more candidates for HD drug development brighten hope for more effective drugs to treat HD.-- Jerry

Posted to HDLighthouse: 16Jul02 HDL Update: Proteins Downregulated by HD.

Alterations in the Mouse and Human Proteome Caused by Huntington's Disease "Maintaining alpha1-antitrypsin and alphaB-crystallin availability during the course of Huntington's disease might prevent neuronal cell death and therefore could be useful in delaying the disease progression." Mol Cell Proteomics 2002 May;1(5):366-75

Huntington's disease is an autosomal dominantly inherited disease that usually starts in midlife.

In our effort to identify proteins involved in processes upstream or downstream of the disease-causing huntingtin, we studied the proteome of a well established mouse model by large gel two-dimensional electrophoresis.[A way to separate and identify proteins]

We could demonstrate for the first time at the protein level that alpha1-antitrypsin and alphaB-crystalline both decrease in expression over the course of disease. Importantly, the alpha1-antitrypsin decrease in the brain precedes that in liver and testes in mice.

Reduced expression of the serine protease inhibitors alpha1-antitrypsin and contraspin was found in liver, heart, and testes close to terminal disease. Decreased expression of the chaperone alphaB-crystallin was found exclusively in the brain.

In three brain regions obtained post-mortem from Huntington's disease patients, alpha1-antitrypsin expression was also altered.

Reduced expression of the major urinary proteins not found in the brain was seen in the liver of affected mice, demonstrating that the disease exerts its influence outside the brain of transgenic mice at the protein level.

Maintaining alpha1-antitrypsin and alphaB-crystallin availability during the course of Huntington's disease might prevent neuronal cell death and therefore could be useful in delaying the disease progression.

Source:Adapted from Mol Cell Proteomics 2002 May;1(5):366-75 Zabel C, Chamrad DC, Priller J, Woodman B, Meyer HE, Bates GP, Klose J.
Institut fur Humangenetik, Universitatsklinikum Charite, 13353 Berlin, Germany. at source -- 16 Jul 2002

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