Characterization of the novel protein P9TLDR (temporal lobe down-regulated) with a brain-site-specific gene expression modality in Alzheimer’s disease brain

• Published in: FEBS letters Vol. 586; no. 24; pp. 4357 - 4361
• Main Authors: Yokota, Tomoko, Akatsu, Hiroyasu, Miyauchi, Takashi, Heese, Klaus
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 14.12.2012
• Subjects: Aged; Alzheimer disease; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid; Amyloid beta-Peptides - metabolism; Brain; cognition; complementary DNA; cortex; Female; gene expression; Gene Expression Regulation; genes; Humans; Mapt; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurodegeneration; neurodegenerative diseases; neurons; Neurotoxicity; Phosphorylation; polymerase chain reaction; protein phosphorylation; signal transduction; suppression subtractive hybridization; Tau; tau Proteins - metabolism; Temporal Lobe - metabolism; Brain; Neurotoxicity; Alzheimer’s disease; Neurodegeneration; Tau; Amyloid; Mapt
• ISSN: 0014-5793; 1873-3468; 1873-3468
• DOI: 10.1016/j.febslet.2012.10.050

► P9TLDR is inhibited in Alzheimer’s disease. ► P9TLDR is implicated in neuro-regenerative processes. ► P9TLDR contributes to higher brain functions. Alzheimer’s disease (AD) is an aging-related neurodegenerative disorder characterized by irreversible loss of higher cognitive functions. The disease is characterized by the presence of amyloid plaques and neurofibrillary tangles (NFT). In the current study we isolated from an intra-cerebral brain-site-specific (AD temporal lobe vs. AD occipital lobe) polymerase chain reaction (PCR)-select cDNA suppression subtractive hybridization (PCR-cDNA-SSH) expression analysis the novel gene P9TLDR, potentially a microtubule-associated protein involved in neuronal migration, with an altered expression pattern: down-regulated in the temporal lobe cortex of early stage AD brains. In an in vitro AD-related cell model, amyloid-β peptide (Aβ)-treated neurons, reduced P9TLDR expression correlated with increased tau protein phosphorylation. In conclusion, interference with the P9TLDR signalling pathways might be a therapeutic strategy for the treatment of AD.