Regional Increase in the Expression of the BCAT Proteins in Alzheimer's Disease Brain: Implications in Glutamate Toxicity

摘要: BACKGROUND The human branched chain aminotransferases (hBCATm, mitochondrial and hBCATc, cytosolic) are major contributors to brain glutamate production. This excitatory neurotransmitter is thought contribute neurotoxicity in neurodegenerative conditions such as Alzheimer's disease (AD) but the expression of hBCAT this has not previously been investigated. OBJECTIVE The objective investigating gain insight into potential metabolic pathways that may be dysregulated AD brain, which would toxicity. METHODS Western blot analysis immunohistochemistry were used determine localization postmortem frontal temporal cortex from matched control brains. RESULTS Western demonstrated a significant regional increase hBCATc hippocampus (↑ 36%; p-values 0.012), with an ↑ 160% reported for hBCATm (p-values = 4.22 × 10-4 2.79 10-5, respectively) relative controls, evidence post-translational modifications hBCATm, more prominent samples. Using immunohistochemistry, immunopositive labelling was observed CA1 CA4 region 0.011 0.026, correlating western analysis. Moreover, level correlated significantly severity, indicated by Braak staging 5.63 10-6 9.29 respectively). CONCLUSION The proteins elevated brain. modulate production toxicity, thereby play role pathogenesis disease.