Expression patterns of chaperone proteins in cerebral cortex of the fetus with Down Syndrome: dysregulation of T-complex protein 1

Chaperone proteins reduce stress-induced denaturation and aggregation of in tracellular proteins and exert protective actions by interfering with the s tress-induced apoptotic pathway in the neuronal cells. Although many studie s have focused on the critical role of chaperones in protein folding and th eir relevance in protein conformational diseases such as Alzheimer's diseas e (AD) and prion disease, limited information is available on their express ion pattern in AD-related disease, Down Syndrome (DS). In a previous study, we reported differentially expressed molecular chapero ne proteins in the brains of adult DS patients. This report demonstrated th e relevance of the aberrant expression patterns to biochemical and neuropat hological abnormalities in adult DS brain. To investigate whether this aberrant expression patterns already exist in s econd trimester DS brain, we performed two-dimensional polyacrylamide gel e lectrophoresis (2-DE) and matrix-associated laser desorption ionization mas s spectroscopy (MALDI-MS) using fetal DS brain. We unambiguously identified and quantified twelve heat shock proteins (HSPs), three glucose regulated proteins (GRPs) and eight T-complex 1 (TCP-1) subunits. Unlike in adult bra in with DS, these studies provide evidence for the normal response of most molecular chaperone proteins at the given time point of DS brain developmen t. However, chaperonin protein TCP-1 alpha and beta subunits showed a signi ficant decrease (P < 0.05) in second trimester brain with DS. Comparable response of chaperone proteins in fetal DS brain suggests that n ot heat-shock induced proteins but rather chaperonin protein TCP-1 may cont ribute significantly to neuropathogenesis in the early second trimester DS brain. This study extends observations of distinct expression patterns of molecula r chaperones in DS brain and we discuss the relevance of aberrant TCP-1 exp ression patterns to developmental DS brain at the early stage.