Abstract

The overall goal of this project is to understand the molecular and cellular changes underlying the aging process by studying two abnormal forms of aspartyl residues in the protein, namely, L-isoAsp and D-Asp, and protein carboxyl methlytransferase (PCMT), a putative enzyme which repairs these damaged residue.
Specific aims are: (1) to measure the levels of protein bound L-isoAsp and D-Asp in particulate fraction of human and rodent brain proteins as a function of age; (2) to determine the methyl accepting capacities of brain praticulate fraction for PCMT; (3) to purity paired helical filaments from Alzheimer brain and determine the ratio of D-Asp/L-Asp in the filament as a function of age; (4) to purify calmodulin and synapsin-1 from early adult and aged human brains and compare their methyl-accepting capacities for PCMT; and (5) to determine the PCMT isozyme patterns in human and rat brain as a function of age.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG000538-13
Application #
3813670
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of California Irvine
Department
Type
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697

  Publications

Sosna, Justyna; Philipp, Stephan; Albay 3rd, Ricardo et al. (2018) Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer's disease. Mol Neurodegener 13:11
Tong, Liqi; Prieto, G Aleph; Cotman, Carl W (2018) IL-1? suppresses cLTP-induced surface expression of GluA1 and actin polymerization via ceramide-mediated Src activation. J Neuroinflammation 15:127
Hainsworth, A H; Lee, S; Foot, P et al. (2018) Super-resolution imaging of subcortical white matter using stochastic optical reconstruction microscopy (STORM) and super-resolution optical fluctuation imaging (SOFI). Neuropathol Appl Neurobiol 44:417-426
Krotee, Pascal; Griner, Sarah L; Sawaya, Michael R et al. (2018) Common fibrillar spines of amyloid-? and human islet amyloid polypeptide revealed by microelectron diffraction and structure-based inhibitors. J Biol Chem 293:2888-2902
Prieto, G Aleph; Tong, Liqi; Smith, Erica D et al. (2018) TNF? and IL-1? but not IL-18 Suppresses Hippocampal Long-Term Potentiation Directly at the Synapse. Neurochem Res :
Prieto, G Aleph; Cotman, Carl W (2017) On the road towards the global analysis of human synapses. Neural Regen Res 12:1586-1589
Chen, E Y; Chu, S; Gov, L et al. (2017) CD200 modulates macrophage cytokine secretion and phagocytosis in response to poly(lactic co-glycolic acid) microparticles and films. J Mater Chem B 5:1574-1584
Snigdha, Shikha; Yassa, Michael A; deRivera, Christina et al. (2017) Pattern separation and goal-directed behavior in the aged canine. Learn Mem 24:123-131
Hernandez, Michael X; Namiranian, Pouya; Nguyen, Eric et al. (2017) C5a Increases the Injury to Primary Neurons Elicited by Fibrillar Amyloid Beta. ASN Neuro 9:1759091416687871
Hatami, Asa; Monjazeb, Sanaz; Milton, Saskia et al. (2017) Familial Alzheimer's Disease Mutations within the Amyloid Precursor Protein Alter the Aggregation and Conformation of the Amyloid-? Peptide. J Biol Chem 292:3172-3185

Showing the most recent 10 out of 281 publications