Brain t-complex polypeptide 1 (TCP- 1) related to its natural substrate beta1 tubulin is decreased in Alzheimer's disease.

Abstract

The t-complex polypeptide 1 is a selective molecular chaperone in tubulin biogenesis, by that nascent tubulin subunits are bound to t-complex polypeptide 1 and released in assembly competent forms. In neurodegenerative diseases with Alzheimer pathology cytoskeletal proteins are deficient and aggregated. Therefore we examined t-complex polypeptide 1 as represented by the zeta subunit and its specific substrate beta 1 tubulin represented by a truncated product in six brain regions of nine patients with Alzheimer's disease, nine patients with Down syndrome and nine controls. We used 2 dimensional electrophoresis with in-gel-digestion and matrix-assisted laser desorption/ ionization- mass spectrometry for the separation and identification of human brain t-complex polypeptide 1 and beta 1 tubulin. When t-complex polypeptide I was related to its natural and specific substrate beta 1 tubulin, the ratio was significantly decreased in the temporal, frontal, parietal cortex and in thalamus of patients with Alzheimer's disease. In Down syndrome the t-complex polypeptide 1/beta 1 tubulin ratio was significantly increased in frontal and parietal cortex suggesting a different mechanism for aggregation of microfilament proteins e.g. beta 1 tubulin. Relatively decreased molecular chaperoning of beta 1 tubulin by t-complex polypeptide 1 may lead to misfolded tubulin aggregating and accumulating in plaques and tangles, a hallmark of Alzheimer's disease. Our contribution provides first clues for a mechanism of microtubular accumulation in Alzheimer's disease and challenges further studies on different chaperones and chaperonins in the brain of patients with neurodegenerative diseases.

• Authors: E Schuller, T Gulesserian, R Seidl, N Cairns, G Lube
• Journal: Life sciences (Life Sci) Vol. 69 Issue 3 Pg. 263-70 (Jun 08 2001) ISSN: 0024-3205 [Print] Netherlands
• PMID: 11441917 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tubulin
• Chaperonin Containing TCP-1
• Chaperonins

Topics

• Alzheimer Disease (metabolism, pathology)
• Brain (metabolism, pathology)
• Chaperonin Containing TCP-1
• Chaperonins (metabolism)
• Down Syndrome (metabolism, pathology)
• Electrophoresis, Polyacrylamide Gel
• Humans
• Image Processing, Computer-Assisted
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Substrate Specificity
• Tubulin (metabolism)