Abstract

We have observed that polysomes isolated from the frontal cortex of AD cases exhibit lower protein synthetic activity. The reduced activity appears to be due to inhibition of both the initiation and elongation steps, which has been characterized for various cells under a number of stresses. We propose that the reduction in polysome function is regulated by alterations in the phosphorylation of specific proteins known to modulate protein synthesis. The investigation will directly assay the phosphorylation states in control and AD postmortem tissues of various initiation factors with immunoblots and ribosomal protein S6. In addition, endogenous kinase and phosphatase activities affecting eIF-2a, S6, tRNA synthetases, and other proteins in the polysome fraction will be compared in the two tissues. The goal of the investigation will be to identify differences in protein phosphorylations that are associated specifically with protein synthesis in the AD tissues.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
5P50AG005138-09
Application #
3790099
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Mount Sinai School of Medicine
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Wang, Jen-Chyong; Alinaghi, Somayeh; Tafakhori, Abbas et al. (2018) Genetic screening in two Iranian families with early-onset Alzheimer's disease identified a novel PSEN1 mutation. Neurobiol Aging 62:244.e15-244.e17
Crum, Jana; Wilson, Jeffrey; Sabbagh, Marwan (2018) Does taking statins affect the pathological burden in autopsy-confirmed Alzheimer's dementia? Alzheimers Res Ther 10:104
Wang, Qi; Guo, Lei; Thompson, Paul M et al. (2018) The Added Value of Diffusion-Weighted MRI-Derived Structural Connectome in Evaluating Mild Cognitive Impairment: A Multi-Cohort Validation1. J Alzheimers Dis 64:149-169
Burke, Shanna L; Cadet, Tamara; Maddux, Marlaina (2018) Chronic Health Illnesses as Predictors of Mild Cognitive Impairment Among African American Older Adults. J Natl Med Assoc 110:314-325
Girdhar, Kiran; Hoffman, Gabriel E; Jiang, Yan et al. (2018) Cell-specific histone modification maps in the human frontal lobe link schizophrenia risk to the neuronal epigenome. Nat Neurosci 21:1126-1136
Kamara, Dennis M; Gangishetti, Umesh; Gearing, Marla et al. (2018) Cerebral Amyloid Angiopathy: Similarity in African-Americans and Caucasians with Alzheimer's Disease. J Alzheimers Dis 62:1815-1826
Wang, Tingyan; Qiu, Robin G; Yu, Ming (2018) Predictive Modeling of the Progression of Alzheimer's Disease with Recurrent Neural Networks. Sci Rep 8:9161
Huang, Qian; Voloudakis, Georgios; Ren, Yimin et al. (2018) Presenilin1/?-secretase protects neurons from glucose deprivation-induced death by regulating miR-212 and PEA15. FASEB J 32:243-253
Hauberg, Mads E; Fullard, John F; Zhu, Lingxue et al. (2018) Differential activity of transcribed enhancers in the prefrontal cortex of 537 cases with schizophrenia and controls. Mol Psychiatry :
Giambartolomei, Claudia; Zhenli Liu, Jimmy; Zhang, Wen et al. (2018) A Bayesian framework for multiple trait colocalization from summary association statistics. Bioinformatics 34:2538-2545

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