Brain alpha-amylase: a novel energy regulator important in Alzheimer disease?
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ABSTRACT:
SUBMITTER: Byman E
PROVIDER: S-EPMC8028266 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Alpha-amylase, the major form of amylase with secondary carbohydrate binding sites, is a crucial enzyme throughout the growth period and life cycle of angiosperm. In rice, alpha-amylase isozymes are critical for the formation of the storage starch granule during seed maturation and motivate the stored starch to nourish the developing seedling during seed germination which will directly affect the plant growth and field yield. Alpha-amylase has not yet been studied intensely to understand its classification, structure, expression trait, and expression regulation in rice and other crops. Among the 10-rice alpha-amylases, most were exclusively expressed in the developing seed embryo and induced in the seed germination process. During rice seed germination, the expression of alpha-amylase genes is known to be regulated negatively by sugar in embryos, however positively by gibberellin (GA) in endosperm through competitively binding to the specific promoter domain; besides, it is also controlled by a series of other abiotic or biotic factors, such as salinity. In this review, we overviewed the research progress of alpha-amylase with focus on seed germination and reflected on how in-depth work might elucidate its regulation and facilitate crop breeding as an efficient biomarker.
| S-EPMC6359163 | biostudies-literature
Project description:The enigma that is Alzheimer's disease (AD) continues to present daunting challenges for effective therapeutic intervention. The lack of disease-modifying therapies may, in part, be attributable to the narrow research focus employed to understand this complex disease. Most studies into disease pathogenesis are based on a priori assumptions about the role of AD lesion-associated proteins such as amyloid-? and tau. However, the complex disease processes at work may not be amenable to single-target therapeutic approaches. Genome-wide expression studies provide an unbiased approach for investigating the pathogenesis of complex diseases like AD. A growing literature suggests a role for cerebrovascular contributions to the pathogenesis of AD. The objective of the current study is to examine human brain microvessels isolated from AD patients and controls by microarray analysis. Differentially expressed genes with more than 2-fold change are used for further data analysis. Gene ontology analysis and pathway analysis algorithms within GeneSpringGX are employed to understand the regulatory networks of differentially expressed genes. Twelve matched pairs of AD and control brain microvessel samples are hybridized to Agilent Human 4 × 44 K arrays in replication. We document that more than 2,000 genes are differentially altered in AD microvessels and that a large number of these genes map to pathways associated with immune and inflammatory response, signal transduction, and nervous system development and function categories. These data may help elucidate heretofore unknown molecular alterations in the AD cerebromicrovasculature. Two condition experiment, diseased vs normal, our study included 12 pairs of biological replicates and each pair was repeated with dye swap making total of 24 double channel hybridizations. we excluded 4 samples for not passing QC. So 20 samples were included in the data analysis.
2013-03-29 | E-GEOD-45596 | biostudies-arrayexpress
Project description:The structures of Aspergillus oryzae α-amylase were determined in a tetragonal crystal, having one molecule as asymmetric unit, and a monoclinic crystal with two molecules as asymmetric unit. Both crystal forms were obtained from trace contaminants of an old commercial lipase preparation. Structures were determined and refined to 1.65 Å and 1.43 Å resolution respectively. The latter crystal has a non-crystallographic (NCS) twofold axis within the asymmetric unit. Glycosylation at Asn197 is evident, and in the tetragonal crystal can be seen to include three, partially disordered sugar residues following the initial N-acetyl glucosamine (NAG). Superposition of the tetragonal crystal model on the α-amylases from Bacillus subtilis (PDB:1BAG), pig pancreas (PDB:3L2L), and barley (PDB:1AMY), show a high degree of coincidence, particularly for the (β/α)8-barrel domains, and especially within the active site. Using this structural agreement between amylases, we extrapolated the binding model of a six residue, limit dextrin found in pig pancreas α-amylase to the A. oryzae enzyme model, which predicts substrate interacting amino acid residues.
| S-EPMC8187280 | biostudies-literature
Project description:The enigma that is Alzheimer's disease (AD) continues to present daunting challenges for effective therapeutic intervention. The lack of disease-modifying therapies may, in part, be attributable to the narrow research focus employed to understand this complex disease. Most studies into disease pathogenesis are based on a priori assumptions about the role of AD lesion-associated proteins such as amyloid-β and tau. However, the complex disease processes at work may not be amenable to single-target therapeutic approaches. Genome-wide expression studies provide an unbiased approach for investigating the pathogenesis of complex diseases like AD. A growing literature suggests a role for cerebrovascular contributions to the pathogenesis of AD. The objective of the current study is to examine human brain microvessels isolated from AD patients and controls by microarray analysis. Differentially expressed genes with more than 2-fold change are used for further data analysis. Gene ontology analysis and pathway analysis algorithms within GeneSpringGX are employed to understand the regulatory networks of differentially expressed genes. Twelve matched pairs of AD and control brain microvessel samples are hybridized to Agilent Human 4 × 44 K arrays in replication. We document that more than 2,000 genes are differentially altered in AD microvessels and that a large number of these genes map to pathways associated with immune and inflammatory response, signal transduction, and nervous system development and function categories. These data may help elucidate heretofore unknown molecular alterations in the AD cerebromicrovasculature.
2013-03-29 | GSE45596 | GEO
Project description:Alzheimer Disease (AD) is a progressive neurological disorder characterized by the deposition of amyloid beta (Aβ), predominantly the Aβ1-42 form, in the brain. Mitochondrial dysfunction and impaired energy metabolism are important components of AD pathogenesis. However, the causal and temporal relationships between them and AD pathology remain unclear. Using a novel C. elegans AD strain with constitutive neuronal Aβ1-42 expression that displays neuromuscular defects and age-dependent behavioural dysfunction reminiscent of AD, we have shown that mitochondrial bioenergetic deficit is an early event in AD pathogenesis, preceding dysfunction of mitochondrial electron transfer chain (ETC) complexes and the onset of global metabolic failure. These results are consistent with an emerging view that AD may be a metabolic neurodegenerative disease, and also confirm that Aβ-driven metabolic and mitochondrial effects can be reproduced in organisms separated by large evolutionary distances.
| S-EPMC5031964 | biostudies-literature
Project description:ObjectiveRecent genome-wide association studies (GWAS) of late-onset Alzheimer disease (LOAD) identified 9 novel risk loci. Discovery of functional variants within genes at these loci is required to confirm their role in Alzheimer disease (AD). Single nucleotide polymorphisms that influence gene expression (eSNPs) constitute an important class of functional variants. We therefore investigated the influence of the novel LOAD risk loci on human brain gene expression.MethodsWe measured gene expression levels in the cerebellum and temporal cortex of autopsied AD subjects and those with other brain pathologies (∼400 total subjects). To determine whether any of the novel LOAD risk variants are eSNPs, we tested their cis-association with expression of 6 nearby LOAD candidate genes detectable in human brain (ABCA7, BIN1, CLU, MS4A4A, MS4A6A, PICALM) and an additional 13 genes ±100 kb of these SNPs. To identify additional eSNPs that influence brain gene expression levels of the novel candidate LOAD genes, we identified SNPs ±100 kb of their location and tested for cis-associations.ResultsCLU rs11136000 (p = 7.81 × 10(-4)) and MS4A4A rs2304933/rs2304935 (p = 1.48 × 10(-4)-1.86 × 10(-4)) significantly influence temporal cortex expression levels of these genes. The LOAD-protective CLU and risky MS4A4A locus alleles associate with higher brain levels of these genes. There are other cis-variants that significantly influence brain expression of CLU and ABCA7 (p = 4.01 × 10(-5)-9.09 × 10(-9)), some of which also associate with AD risk (p = 2.64 × 10(-2)-6.25 × 10(-5)).ConclusionsCLU and MS4A4A eSNPs may at least partly explain the LOAD risk association at these loci. CLU and ABCA7 may harbor additional strong eSNPs. These results have implications in the search for functional variants at the novel LOAD risk loci.
| S-EPMC3398432 | biostudies-literature
Project description:Alzheimer's disease (AD) is a fatal form of dementia of unknown etiology. Although amyloid plaque accumulation in the brain has been the subject of intensive research in disease pathogenesis and anti-amyloid drug development; the continued failures of the clinical trials suggest that amyloids are not a key cause of AD and new approaches to AD investigation and treatment are needed. We propose a new hypothesis of AD development based on metabolic abnormalities in circulating red blood cells (RBCs) that slow down oxygen release from RBCs into brain tissue which in turn leads to hypoxia-induced brain energy crisis; loss of neurons; and progressive atrophy preceding cognitive dysfunction. This review summarizes current evidence for the erythrocytic hypothesis of AD development and provides new insights into the causes of neurodegeneration offering an innovative way to diagnose and treat this systemic disease.
| S-EPMC7019250 | biostudies-literature
Project description:BackgroundLack of clear understanding remains on the overlapping atrophy patterns of aging and early Alzheimer disease (AD) pathology in gray matter (GM) of the brain in vivo.ObjectiveTo evaluate the independent and overlapping patterns of GM atrophy in normal aging and AD.MethodsA total of 169 cognitively normal subjects and 33 persons with probable AD enrolled in the longitudinal Cardiovascular Health Study-Cognition Study underwent 3-dimensional volumetric MRI scans. Controls remained cognitively normal for at least 5 years after their MRI scans and the probable AD subjects were relatively early in their clinical course with an average modified Mini-Mental State Examination score of 76/100. The scans were analyzed using voxel-based morphometry adjusting for total intracranial volume, gender, education, and race.ResultsWith older age, GM volume was lower in the sensorimotor and heteromodal association areas in frontal, temporal, occipital, and parietal lobes, as well as in the cerebellum (false discovery rate p = 0.05). Additional atrophy was observed in the posterior hippocampus, thalamus, and middle cingulate gyrus. By contrast, atrophy was seen in subjects with AD in the anterior hippocampal/parahippocampal regions and the precuneus. Normal aging and AD overlapped in the hippocampal body and the entorhinal cortex.ConclusionBrain atrophy with aging was observed in supratentorial and infratentorial areas, as well in primary motor, sensory, and heteromodal association regions. Age and Alzheimer disease exert independent gray matter atrophy patterns but these effects overlapped substantially in the hippocampus and entorhinal cortex.
| S-EPMC2788799 | biostudies-literature
Project description:The gene aml encoding alpha-amylase in Streptomyces lividans was cloned in the multicopy plasmid pIJ486, generating plasmid pAMI11. Plasmid pAMI11 and pIJ486 were propagated in S. lividans TK21 to obtain S. lividans TK21(pAMI11) and its isogenic strain S. lividans TK21(pIJ486). Transcriptional profiling of the bacterium that overproduces alpha-amylase mainly resulted in the upregulation of genes involved in the biogenesis and function of ribosomes, together with the upregulation of the genes involved in the redox processes, the ABC transporters, the central carbon, aminoacid and purine /pyrimidine metabolism. Moreover, some genes involved in oxidative stress were upregulated. The number of genes downregulated was much lower than the upregulated ones. Therefore, bacteria respond by favouring alpha-amylase overproduction that apparently does not cause damage to the cell.
2015-07-23 | GSE61448 | GEO
Project description:Many patients suffering late-onset Alzheimer disease show a deficit in respiratory complex IV activity. The de novo pyrimidine biosynthesis pathway connects with the mitochondrial respiratory chain upstream from respiratory complex IV. We hypothesized that these patients would have decreased pyrimidine nucleotide levels. Then, different cell processes for which these compounds are essential, such as neuronal membrane generation and maintenance and synapses production, would be compromised. Using a cell model, we show that inhibiting oxidative phosphorylation function reduces neuronal differentiation. Linking these processes to pyrimidine nucleotides, uridine treatment recovers neuronal differentiation. To unmask the importance of these pathways in Alzheimer disease, we firstly confirm the existence of the de novo pyrimidine biosynthesis pathway in adult human brain. Then, we report altered mRNA levels for genes from both de novo pyrimidine biosynthesis and pyrimidine salvage pathways in brain from patients with Alzheimer disease. Thus, uridine supplementation might be used as a therapy for those Alzheimer disease patients with low respiratory complex IV activity.
| S-EPMC6814620 | biostudies-literature