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 #
2P50AG005138-06
Application #
3813970
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1989
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

Barnes, Josephine; Bartlett, Jonathan W; Wolk, David A et al. (2018) Disease Course Varies According to Age and Symptom Length in Alzheimer's Disease. J Alzheimers Dis 64:631-642
Gandal, Michael J; Haney, Jillian R; Parikshak, Neelroop N et al. (2018) Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap. Science 359:693-697
Huckins, L M; Hatzikotoulas, K; Southam, L et al. (2018) Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa. Mol Psychiatry 23:1169-1180
Schaffert, Jeff; LoBue, Christian; White, Charles L et al. (2018) Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer's disease. Neuropsychology 32:410-416
Ki?emet-Piska?, Spomenka; Babi? Leko, Mirjana; Blažekovi?, Antonela et al. (2018) Evaluation of cerebrospinal fluid phosphorylated tau231 as a biomarker in the differential diagnosis of Alzheimer's disease and vascular dementia. CNS Neurosci Ther 24:734-740
Soleimani, Laili; Ravona-Springer, Ramit; Heymann, Anthony et al. (2018) Depression is more strongly associated with cognition in elderly women than men with type 2 diabetes. Int Psychogeriatr :1-5
Burke, Shanna L; Maramaldi, Peter; Cadet, Tamara et al. (2018) Decreasing hazards of Alzheimer's disease with the use of antidepressants: mitigating the risk of depression and apolipoprotein E. Int J Geriatr Psychiatry 33:200-211
Audrain, Mickael; Haure-Mirande, Jean-Vianney; Wang, Minghui et al. (2018) Integrative approach to sporadic Alzheimer's disease: deficiency of TYROBP in a tauopathy mouse model reduces C1q and normalizes clinical phenotype while increasing spread and state of phosphorylation of tau. Mol Psychiatry :
Boban, Mirta; Babi? Leko, Mirjana; Miški?, Terezija et al. (2018) Human neuroblastoma SH-SY5Y cells treated with okadaic acid express phosphorylated high molecular weight tau-immunoreactive protein species. J Neurosci Methods :
Zhu, Carolyn W; Grossman, Hillel; Neugroschl, Judith et al. (2018) A randomized, double-blind, placebo-controlled trial of resveratrol with glucose and malate (RGM) to slow the progression of Alzheimer's disease: A pilot study. Alzheimers Dement (N Y) 4:609-616

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