Brain t-complex polypeptide 1 (TCP-1) related to its natural substrate β1 tubulin is decreased in Alzheimer's disease

• Published in: Life sciences (1973) Vol. 69; no. 3; pp. 263 - 270
• Main Authors: Schuller, Elisabeth, Gulesserian, Talin, Seidl, Rainer, Cairns, Nigel, Lubec, Gert
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 08.06.2001
• Subjects: 2 Dimensional gel electrophoresis; Alzheimer's disease; Eukaryotic cytoplasmic chaperonine; Molecular chaperone; Neurodegenerative disease; T-complex polypeptide 1; Neurodegenerative disease; 2 Dimensional gel electrophoresis; T-complex polypeptide 1; Alzheimer's disease; Eukaryotic cytoplasmic chaperonine; Molecular chaperone
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(01)01126-2

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 β 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 β 1 tubulin. When t-complex polypeptide 1 was related to its natural and specific substrate β 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/β 1 tubulin ratio was significantly increased in frontal and parietal cortex suggesting a different mechanism for aggregation of microfilament proteins e.g. β 1 tubulin. Relatively decreased molecular chaperoning of β 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.