Aspartoacylase/aminoacylase II (ASPA/ACY II) is mainly synthesized in oligodendrocytes to contribute in myelin synthesis. Although axonal damage is seen in the brain with human immunodeficiency virus encephalitis (HIVE), ASPA contribution in the pathology is not known. Immunostaining study showed that ASPA protein is reduced in the white matter of patients with HIVE compared to the control.
View Article and Find Full Text PDFN-acetylaspartic acid (NAA) is predominantly present in brain and also present in lower amount in peripheral organs. The role of NAA in pathophysiology is poorly understood. Therefore the review was aimed to understand contribution of NAA in disease process.
View Article and Find Full Text PDFAtaxia Telangiectasia (A-T) is an inherited immunodeficiency disorder wherein mutation of the ATM kinase is responsible for the A-T pathogenesis. Although the precise role of ATM in A-T pathogenesis is still unclear, its function in responding to DNA damage has been well established. Here we demonstrate that in addition to its role in DNA repair, ATM also regulates proteasome-mediated protein turnover through suppression of the ISG15 pathway.
View Article and Find Full Text PDFAstrocytes play an important role in astrocyte-neuron homeostasis. In HIV-1-infected brain, interleukin 1 beta (IL-1β) activation of astrocytes contributes to neurodegeneration. However, the molecular mechanisms underlying IL-1β-activated-astrocytes-induced neurodegeneration in HIV-1-infected brain are largely unknown.
View Article and Find Full Text PDFAspartoacylase (ASPA) converts N-acetylaspartic acid into aspartate and acetate. In Canavan disease (CD), N-acetylaspartic acid (NAA) is found to be increased and over 65 mutations including IVS4+1 G → T, deletion of introns and exons have been reported in the ASPA gene. These changes lead to severe form or mild form of CD.
View Article and Find Full Text PDFParkinson's disease (PD) is a neurodegenerative disorder, caused by reduced levels of catecholamines and oxidative stress. Symptoms seen in the disease include tremor, rigidity, bradykinesia and postural disability. Oxidative stress plays a key role in neurodegeneration and motor abnormalities seen in PD.
View Article and Find Full Text PDFEthnopharmacological Relevance: Withania somnifera root extract (Ws)/Ashwagandha/Indian ginseng is a traditional herbal medicine, used over 4000 years in India, shown to have effect on neural growth and locomotor function. Although catecholamines and oxidative stress resulting in neurodegeneration and locomotor disorder are the main events in Parkinson's disease (PD), efficacy of the drug on these molecules and physiological abnormality are not clear.
Aim Of The Study: The objective of the study was to examine effect of Ws on catecholamines and physiological abnormalities seen in PD using PD model mouse.
Parkinson's disease (PD) is a neurodegenerative disorder that leads to impairment of balance and coordination. Therapy for the disease is still under investigation. Withania somnifera (A-Extract), a herbal medicine, has been known for a spectrum of health-promoting effects including activation of immune, muscle and neuronal systems.
View Article and Find Full Text PDFIn intestinal cells, arginine (Arg) is 1 of the 2 most potent amino acid activators of p70(s6k), a key regulator of 5'- terminal oligopyrimidine mRNA translation, a necessary condition for increased cell migration. To investigate the mechanism of response to Arg, we used the rat crypt cell line cdx2-transformed IEC-6 cells (cdx2-IEC) and measured cell migration, immunocytochemical analysis of p70(s6k) activation in response to Arg, and production of nitric oxide (NO). When treated with Arg, cdx2-IEC increased in phosphorylation on Thr-389 of p70(s6k) (pp70(s6k)) compared with control (P < 0.
View Article and Find Full Text PDFN-acetylaspartic acid (NAA) is converted into aspartate and acetate by aspartoacylase. Abnormal levels of the enzyme leads to accumulation of NAA and these changes have been observed in Canavan disease and type 2 diabetes. How upregulation of NAA affect the gastrointestine protein levels and the function is not known.
View Article and Find Full Text PDFTetrahydrobiopterin (BH4) is a co-factor that enhances the activity of other enzymes, and this co-factor level is found to be affected in phenylketonuria (PKU), an amino acid metabolism disorder. The present study was aimed at understanding the effect of BH4 on mutations in the regulatory domain of phenylalanine hydroxylase (PAH). Among 14 patients, 5 patients were classical PKU, 3 were atypical PKU, and 6 were mild PKU.
View Article and Find Full Text PDFThe Spontaneously Epileptic Rat (SER), a double-mutant for tremor and zitter mutations, shows spontaneous occurrences of absence-like and tonic seizures. Several lines of evidence suggest that the combined effect of Aspa and Atrn mutations is the most likely cause of the epileptic phenotype of the SER. To address this issue, we produced a new double-mutant mouse line carrying both homozygous Aspa-knockout and Atrn(mg-3J) mutant alleles.
View Article and Find Full Text PDFPompe disease (glycogen storage disease type II) is a glycogen storage disease caused by a deficiency of the lysosomal enzyme, acid maltase/acid alpha-1,4 glucosidase (GAA). Deficiency of the enzyme leads primarily to intra-lysosomal glycogen accumulation, primarily in cardiac and skeletal muscles, due to the inability of converting glycogen into glucose. Enzyme replacement therapy (ERT) has been applied to replace the deficient enzyme and to restore the lost function.
View Article and Find Full Text PDFCanavan disease (CD) is an autosomal recessive disorder, characterized by spongy degeneration of the brain. Patients with CD have aspartoacylase (ASPA) deficiency, which results accumulation of N-acetylaspartic acid (NAA) in the brain and elevated excretion of urinary NAA. Clinically, patients with CD have macrocephaly, mental retardation and hypotonia.
View Article and Find Full Text PDFAspartoacylase (ASPA) hydrolyzes N-acetylaspartic acid (NAA) into aspartate and acetate. Normal hydrolysis of NAA is important to maintain healthy neurons. Since enteric neuropathy is one of the events seen in diabetes, whether ASPA activity is affected in diabetic condition is not known.
View Article and Find Full Text PDFType 2 diabetes caused by obesity shows autonomic neuropathy. Molecular mechanism involved in enteric neurodegeneration is not clear. Neuronal nitric oxide synthase (nNOS) is one of the important agents involved in gastrointestinal function.
View Article and Find Full Text PDFPhenylketonuria (PKU) is an inborn error of amino acid metabolism. Phenylalanine hydroxylase (PAH) mutations resulting reduced enzyme levels lead to accumulation of phenylalanine (Phe) in brain, if Phe diet is not restricted. Patients with PKU show neurophysiological abnormalities including demyelination and cognitive defect.
View Article and Find Full Text PDFCanavan disease (CD) is an autosomal recessive disorder caused by aspartoacylase (ASPA) gene mutations resulting enzyme deficiency. The homozygous knockout mouse for CD showed symptoms similar observed in patients with CD. Canavan disease leads to early death.
View Article and Find Full Text PDFPhenylketonuria (PKU) is an inborn error of amino acid metabolism. Phenylalanine hydroxylase (PAH) deficiency results in accumulation of phenylalanine (Phe) in the brain and leads to pathophysiological abnormalities including cognitive defect, if Phe diet is not restricted. Neuronatin and 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) reportedly have role in memory.
View Article and Find Full Text PDFCanavan's disease (CD) is a fatal, hereditary disorder of CNS development that has been linked to mutations in the gene for the enzyme aspartoacylase (ASPA) (EC 3.5.1.
View Article and Find Full Text PDFCanavan disease (CD) is a neurodegenerative disorder characterized by the spongy degeneration of the white matter of the brain. Aspartoacylase (ASPA) gene mutation resulting enzyme deficiency is the basic cause of CD. Whether the ASPA defect in CD affects the spinal cord has been investigated using the ASPA gene knockout mouse.
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