ORCID Profile
0000-0001-6838-0386
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Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.PNEUROBIO.2005.07.001
Abstract: Transcriptomics and proteomics are increasingly applied to gain a mechanistic insight into neurodegenerative disorders. These techniques not only identify distinct, differentially expressed mRNAs and proteins but are also employed to dissect signaling pathways and reveal networks by using an integrated approach. In part I of this back-to-back review, technical aspects are discussed: in the transcriptomics section, which includes enrichment by laser microcapture dissection, we comment on qRT-PCR, SAGE, subtractive hybridization, differential display and microarrays, including software packages. In the proteomics section we discuss two-dimensional (2D) gel electrophoresis, liquid chromatography, methods to label and enrich specific proteins or peptides, and different types of mass spectrometers. These tools have been applied to a range of neurodegenerative disorders and are discussed and integrated in part II (Functional Genomics meets neurodegenerative disorders. Part II: application and data integration).
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.PNEUROBIO.2005.07.002
Abstract: The transcriptomic and proteomic techniques presented in part I (Functional Genomics meets neurodegenerative disorders. Part I: transcriptomic and proteomic technology) of this back-to-back review have been applied to a range of neurodegenerative disorders, including Huntington's disease (HD), Prion diseases (PrD), Creutzfeldt-Jakob disease, amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), frontotemporal dementia (FTD) and Parkinson's disease (PD). S les have been derived either from human brain and cerebrospinal fluid, tissue culture cells or brains and spinal cord of experimental animal models. With the availability of huge data sets it will firstly be a major challenge to extract meaningful information and secondly, not to obtain contradicting results when data are collected in parallel from the same source of biological specimen using different techniques. Reliability of the data highly depends on proper normalization and validation both of which are discussed together with an outlook on developments that can be anticipated in the future and are expected to fuel the field. The new insight undoubtedly will lead to a redefinition and sub ision of disease entities based on biochemical criteria rather than the clinical presentation. This will have important implications for treatment strategies.
Publisher: S. Karger AG
Date: 2008
DOI: 10.1159/000113696
Abstract: i Background: /i Alzheimer’s disease (AD) is characterized by β-amyloid (Aβ) peptide-containing plaques and tau-containing neurofibrillary tangles. By intracerebral injection of Aβ sub /sub , both pathologies have been combined in P301L tau mutant mice. Furthermore, in cell culture, Aβ sub /sub induces tau aggregation. While both Aβ sub /sub and mutant tau cause neuronal dysfunction, their modes of action are only vaguely understood. i Methods: /i To determine which processes are disrupted by Aβ sub /sub and/or P301L mutant tau, we used transcriptomic and proteomic techniques followed by functional validation and analysis of human AD tissue. i Results: /i Our transcriptomic study in the SH-SY5Y cell culture system revealed that Aβ sub /sub and P301L tau expression independently affect genes controlling the cell cycle and cell proliferation. Proteomics applied to Aβ sub /sub -treated P301L tau-expressing SH-SY5Y cells and the amygdala of Aβ sub /sub -injected P301L transgenic mice revealed that a significant fraction of proteins altered in both systems belonged to the same functional categories, i.e. stress response and metabolism. Among the proteins identified was valosin-containing protein (VCP), a component of the quality control system during endoplasmic reticulum stress. Mutations in VCP have recently been linked to frontotemporal dementia. i Conclusion: /i Our data support the mitosis failure hypothesis that claims that aberrant cell cycle reentry of postmitotic neurons induces apoptosis. Furthermore, our data underline a role of Aβ sub /sub in the stress response associated with protein folding.
Publisher: Oxford University Press (OUP)
Date: 30-04-2007
DOI: 10.1093/HMG/DDM097
Abstract: Little is known about the genes and proteins involved in the process of human memory. To identify genetic factors related to human episodic memory performance, we conducted an ultra-high-density genome-wide screen at > 500 000 single nucleotide polymorphisms (SNPs) in a s le of normal young adults stratified for performance on an episodic recall memory test. Analysis of this data identified SNPs within the calmodulin-binding transcription activator 1 (CAMTA1) gene that were significantly associated with memory performance. A follow up study, focused on the CAMTA1 locus in an independent cohort consisting of cognitively normal young adults, singled out SNP rs4908449 with a P-value of 0.0002 as the most significant associated SNP in the region. These validated genetic findings were further supported by the identification of CAMTA1 transcript enrichment in memory-related human brain regions and through a functional magnetic resonance imaging experiment on in iduals matched for memory performance that identified CAMTA1 allele-specific upregulation of medial temporal lobe brain activity in those in iduals harboring the 'at-risk' allele for poorer memory performance. The CAMTA1 locus encodes a purported transcription factor that interfaces with the calcium-calmodulin system of the cell to alter gene expression patterns. Our validated genomic and functional biological findings described herein suggest a role for CAMTA1 in human episodic memory.
No related grants have been discovered for Frederic Hoerndli.