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Biomedical subjects

M Walzer

Publications and source records attributed to M Walzer.

4 recordsLinked to original sources
PubMed2005

Tau phosphorylation increases in symptomatic mice overexpressing A30P alpha-synuclein.

Mice overexpressing mutant alpha-synuclein develop a progressive loss of motor function associated with the accumulation of aggregated alpha-synuclein in neurons of the brainstem. Recent reports suggest that tau pathology might also be associated with Parkinson disease (PD) and aggregation of alpha-synuclein. We now report that mice overexpressing A30P alpha-synuclein develop abnormally phosphorylated tau in parallel with the accumulation of aggregated alpha-synuclein. Enhanced phosphorylation of tau occurs only in symptomatic mice that also harbor abundant aggregated alpha-synuclein. The increased phosphorylation of tau occurs at S396/404 and S202 as shown by immunoblotting and immunocytochemical studies with the antibodies PHF-1 and AT8. Neurons that accumulated alpha-synuclein occurred in the dorsal brainstem and did not show strong colocalization with neurons that showed abnormal tau phosphorylation, which largely occurred in the ventral brainstem. Aggregation of alpha-synuclein and phosphorylation of tau are associated with increased levels of phosphorylated c-jun kinase (JNK), which is a stress kinase known to phosphorylate tau protein. These results suggest that alpha-synuclein pathology can stimulate early pathological changes in tau.

Age Factors↗
PubMed1982

Treatment of hyperargininaemia due to arginase deficiency with a chemically defined diet.

A brother and sister aged 11 and 17 years have been reported previously to have hyperargininaemia and arginase deficiency: they were treated with a semi-synthetic diet consisting of fat, carbohydrate, minerals, vitamins and essential amino acids in amounts equivalent to 0.55-0.65 g protein kg-1 day-1 for 2 years. Plasma arginine levels fell from 0.50-0.90 mumol/1 to 0.13-0.30 mumol/1 (normal range 0.02-0.15). Increased concentrations of arginine in the cerebrospinal fluid (CSF) fell from 0.069-0.098 mumol/l to 0.040-0.056 mumol/l (normal mean +/- SD = 0.020 +/- 0.006). Dibasic aminoaciduria returned to normal within 1 week. Substitution of the keto-acid analogues of five essential amino acids in the formula lowered arginine concentrations further, but proved to be unpalatable. Urinary concentrations of orotic acid, uridine and uracil fell toward normal but remained increased, even when the plasma ammonia concentration was measured as normal. Both patients showed a stable clinical improvement.

Adolescent↗
PubMedDate not supplied

Oral and subcutaneous administration of the glycosaminoglycan C3 attenuates Abeta(25-35)-induced abnormal tau protein immunoreactivity in rat brain.

High molecular weight glycosaminoglycans (GAG) and proteoglycans (PG) affect pathological changes of the brain in Alzheimer's disease (AD). PG stimulate the processing and aggregation of amyloid-beta (Abeta), protect the protein from proteolysis, and increase the formation of neurofibrillary tangles by inducing the hyperphosphorylation of tau protein. These effects may be competitively inhibited by GAG. We have studied the effects of orally (by gavage) and subcutaneously (s.c.) administered low molecular weight heparin, C3 (4-10 oligosaccharides; MW = 2.1 kDa; USP value = 12 U/mg), on abnormal tau-2 protein immunoreactivity in the rat hippocampus following a single, unilateral intra-amygdaloid administration of Abeta(25-35). Oral administration of C3 (25 mg/kg; once daily) was initiated 3 days prior to Abeta(25-35) administration, and was continued daily for an additional 14 days. S.c. administration of C3 (2.5 mg/kg, twice daily), was started 3 days prior to, and was continued for 32 days after, Abeta(25-35) administration. Animal brains were subsequently processed for tau-2, ChAT-immunoreactivity, choline acetyltransferase (ChAT) activity and acetylcholinesterase (AChE) activity. Both oral and s.c. administration of C3 attenuated Abeta(25-35) induced appearance of tau-2-immunoreactive (IR) perikarya in the ipsilateral hippocampus (P < 0.05). Hippocampal cholinergic enzyme activity in C3 treated animals was not significantly different from control animals. The present findings suggest that C3 might be used successfully to prevent abnormal tau protein formation in chronic neurologic diseases, such as AD. Moreover, our data demonstrate that the mechanism of this effect does not appear to influence the cholinergic system of the brain.

Acetylcholinesterase↗