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 #
5P50AG005138-08
Application #
3802545
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1991
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

Pimenova, Anna A; Raj, Towfique; Goate, Alison M (2018) Untangling Genetic Risk for Alzheimer's Disease. Biol Psychiatry 83:300-310
Kirson, Noam Y; Scott Andrews, J; Desai, Urvi et al. (2018) Patient Characteristics and Outcomes Associated with Receiving an Earlier Versus Later Diagnosis of Probable Alzheimer's Disease. J Alzheimers Dis 61:295-307
Culverhouse, R C; Saccone, N L; Horton, A C et al. (2018) Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. Mol Psychiatry 23:133-142
Edler, Melissa K; Sherwood, Chet C; Meindl, Richard S et al. (2018) Microglia changes associated to Alzheimer's disease pathology in aged chimpanzees. J Comp Neurol 526:2921-2936
Mitchell, A C; Javidfar, B; Pothula, V et al. (2018) MEF2C transcription factor is associated with the genetic and epigenetic risk architecture of schizophrenia and improves cognition in mice. Mol Psychiatry 23:123-132
Weintraub, Sandra; Besser, Lilah; Dodge, Hiroko H et al. (2018) Version 3 of the Alzheimer Disease Centers' Neuropsychological Test Battery in the Uniform Data Set (UDS). Alzheimer Dis Assoc Disord 32:10-17
Munger, Emily L; Edler, Melissa K; Hopkins, William D et al. (2018) Astrocytic changes with aging and Alzheimer's disease-type pathology in chimpanzees. J Comp Neurol :
Wilmoth, Kristin; LoBue, Christian; Clem, Matthew A et al. (2018) Consistency of traumatic brain injury reporting in older adults with and without cognitive impairment. Clin Neuropsychol 32:524-529
Hadjichrysanthou, Christoforos; McRae-McKee, Kevin; Evans, Stephanie et al. (2018) Potential Factors Associated with Cognitive Improvement of Individuals Diagnosed with Mild Cognitive Impairment or Dementia in Longitudinal Studies. J Alzheimers Dis 66:587-600
Mincer, Joshua S; Baxter, Mark G; McCormick, Patrick J et al. (2018) Delineating the Trajectory of Cognitive Recovery From General Anesthesia in Older Adults: Design and Rationale of the TORIE (Trajectory of Recovery in the Elderly) Project. Anesth Analg 126:1675-1683

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