•  17
    Gene structure and organization of the human beta-secretase promoter
    with K. Sambamurti, R. Kinsey, Y. W. Ge, and D. K. Lahiri
    Faseb J 18 1034-6. 2004.
    The first step in the generation of the amyloid-beta peptide deposited in the brains of patients with Alzheimer's disease is the processing of the larger Abeta precursor protein by an integral membrane aspartyl protease named the beta-site APP-cleaving enzyme . We present the genomic organization of the BACE gene. BACE mRNAs are synthesized as nine exons and eight introns from a 30.6 kb region of chromosome 11q23.2-11q23.3. Regulation of BACE may play an important role in regulating the levels o…Read more
  •  18
    The LEARn model: An epigenetic explanation for idiopathic neurobiological diseases
    with Debomoy K. Lahiri and Nasser H. Zawia
    Molecular Psychiatry 14 (11): 992-1003. 2009.
    Neurobiological disorders have diverse manifestations and symptomology. Neurodegenerative disorders, such as Alzheimer's disease, manifest late in life and are characterized by, among other symptoms, progressive loss of synaptic markers. Developmental disorders, such as autism spectrum, appear in childhood. Neuropsychiatric and affective disorders, such as schizophrenia and major depressive disorder, respectively, have broad ranges of age of onset and symptoms. However, all share uncertain etiol…Read more
  •  5
    The goal of genome-wide association studies is to identify SNPs unique to disease. It usually involves a single sampling from subjects' lifetimes. While primary DNA sequence variation influences gene-expression levels, expression is also influenced by epigenetics, including the 'somatic epitype' ), an epigenotype acquired postnatally. While genes are inherited, and novel polymorphisms do not routinely appear, G is fluid. Furthermore, G could respond to environmental factors and to differences in…Read more
  •  36
    Amyloid-beta peptide plaque in the brain is the primary diagnostic criterion of Alzheimer's disease . The physiological role of Abeta are poorly understood. We have previously determined an Abeta interacting domain in the promoters of AD-associated genes . This AbetaID interacts in a DNA sequence-specific manner with Abeta. We now demonstrate novel Abeta activity as a possible transcription factor. Herein, we detected Abeta-chromatin interaction in cell culture by ChIP assay. We observed that hu…Read more
  •  1
    Apolipoprotein E , encoded by the apolipoprotein E gene , plays an important role in the pathogenesis of Alzheimer's disease . The APOE epsilon4 variant is strongly associated with AD. APOE promoter polymorphisms have also been reported to associate with higher AD risk. Mouse models of APOE expression have long been used to study the pathogenesis of AD. Elucidating the role of the APOE gene in AD requires understanding of how its regulation differs between mouse and human APOE genes, and how the…Read more
  •  1
    Early-life events may trigger biochemical pathways for Alzheimer's disease: the "LEARn" model
    with D. K. Lahiri, N. H. Zawia, N. H. Greig, and K. Sambamurti
    Biogerontology 9 375-9. 2008.
    Alzheimer's disease , the most common form of dementia among the elderly, manifests mostly late in adult life. However, it is presently unclear when the disease process starts and how long the pathobiochemical processes take to develop. Our goal is to address the timing and nature of triggers that lead to AD. To explain the etiology of AD, we have recently proposed a "Latent Early-life Associated Regulation" model, which postulates a latent expression of specific genes triggered at the developme…Read more
  •  6
    Deposition of extracellular plaques, primarily consisting of amyloid beta peptide , in the brain is the confirmatory diagnostic of Alzheimer's disease ; however, the physiological and pathological role of Abeta is not fully understood. Herein, we demonstrate novel Abeta activity as a putative transcription factor upon AD-associated genes. We used oligomers from 5'-flanking regions of the apolipoprotein E , Abeta-precursor protein and beta-amyloid site cleaving enzyme-1 genes for electrophoretic …Read more
  •  2
    The beta-amyloid protein present in the neuritic plaques of Alzheimer's disease is cleaved from Abeta precursor protein by beta- and gamma-secretases. Following identification of beta-APP cleaving enzyme as the beta-secretase, a homologous beta-secretase 2 was described. Our goal is to characterize the regulatory region of the BACE genes. We compare functional domains within the BACE1 and BACE2 regulatory regions. Both BACE genes lack canonical TATAand CAAT boxes, but they contain distinguishing…Read more