The accumulation of potentially deleterious L-isoaspartyl linkages in proteins is prevented by the action of protein L-isoaspartyl O-methyltransferase, a widely distributed enzyme that is particularly active in mammalian brain. Methyltransferase-deficient (knock-out) mice exhibit greatly increased levels of isoaspartate and typically succumb to fatal epileptic seizures at 4 -10 weeks of age. The link between isoaspartate accumulation and the neurological abnormalities of these mice is poorly understood. Here, we demonstrate that synapsin I from knock-out mice contains 0.9 ؎ 0.3 mol of isoaspartate/mol of synapsin, whereas the levels in wild-type and heterozygous mice are undetectable. Transgenic mice that selectively express methyltransferase only in neurons show reduced levels of synapsin damage, and the degree of reduction correlates with the phenotype of these mice. Isoaspartate levels in synapsin from the knock-out mice are five to seven times greater than those in the average protein from brain cytosol or from a synaptic vesicle-enriched fraction. The isoaspartyl sites in synapsin from knock-out mice are efficiently repaired in vitro by incubation with purified methyltransferase and S-adenosyl-L-methionine. These findings demonstrate that synapsin I is a major substrate for the isoaspartyl methyltransferase in neurons and suggest that isoaspartate-related alterations in the function of presynaptic proteins may contribute to the neurological abnormalities of mice deficient in this enzyme. Fig. 1, dashed arrows) constitutes a major pathway for spontaneous protein damage at physiological pH and temperature (1-3). The internal ␣-carboxyl characteristic of isoaspartyl sites is selectively methylated by a widely distributed protein L-isoaspartyl O-methyltransferase (PIMT) 2 (4 -6). Considerable evidence suggests that PIMT functions to repair this damage in vivo by the mechanism illustrated in Fig. 1 (solid arrows). PIMT selectively methylates the atypical ␣-carboxyl of the isoAsp site. This is followed immediately by a spontaneous demethylation to form a metastable succinimide. Spontaneous hydrolysis of the succinimide over a time course of 2-4 h generates a normal L-aspartyl site with an efficiency of 15-30%. Purified PIMT catalyzes conversion of isoaspartyl sites to normal Asp-Xaa linkages in synthetic peptides (7-9) and has been shown to restore function to isoaspartate-containing forms of proteins such as calmodulin (10) and the Escherichia coli phosphocarrier protein HPr (11). Pharmacological inhibition of PIMT activity in rat PC12 cells leads to reversible accumulation of isoaspartyl sites in a variety of proteins, including tubulin (12) and histone H2B (13). Formation of isoaspartyl sites (Studies with PIMT-deficient mice further support a repair function for PIMT (14,15). Whereas proteins in extracts from wild-type or heterozygous PIMT mice contain only trace levels of isoaspartate, proteins in extracts from knock-out mice show greatly increased isoaspartate levels in extracts from all tissues examined, w...

No abstract

This study aims to identify the components of comprehensive geriatric assessment (CGA) in older post-stroke patients. A cross-sectional study was conducted on 137 post-stroke patients aged ≥ 60 years old being treated at the National Geriatric Hospital. The components of CGA were assessed as medical status (nutrition; urinary incontinence, frailty, visual and hearing ability); functional status (Barthel index, instrumental activity daily living, risk of fall); neuropsychological status (cognition and depression). 66.4% of patients had an ischemic stroke, and 33.6% of patients had a hemorrhage stroke. In both ischemic and hemorrhagic post-stroke groups, domains such as functional impairment, malnutrition, vision loss, high risk of falls, cognitive impairment, and depression account for a high rate (≥ 50%). There was no statistically significant difference in rates of CGA domains between the two groups of patients with ischemic and hemorrhage stroke. This study showed a high prevalence of most components of CGA in older post-stroke patients both in ischemic stroke and hemorrhage stroke patients.

This study was conducted to assess the association between risk of fall and relating factors in osteoporosis patients at the National Geriatrics Hospital. This is a cross-sectional study on 141 osteoporotic patients aged ≥ 60 years old examined or treated at the National Geriatric Hospital. Data were collected by using designed tools including characteristics of these patients. We entered data on Redcap and used SPSS version 22.0 for analysis. The mean age and standard deviation were 73.12 (8.62) with female patients accounted for majority with 94.3%. The mean age of patients with high risk of falls was higher than patients with low risk of falling (with p < 0.05). Heart failure and diabetes mellitus were associated with the risk of falls in older patients with osteoporosis (p < 0.05). The mean Charlson Index and mean number of diseases in the group of patients at high risk of falls were higher than in the group of patients with low risk of falls (with p < 0.05). The study showed that advanced age, heart failure, diabetes, and depression were significantly associated with a higher risk of falls in older patients with osteoporosis.