ArticleCell death & disease2014
Altered expression of Alzheimer's disease-related genes in the cerebellum of autistic patients: a model for disrupted brain connectome and therapy.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
36 citing papers in PubMed, 67 citations in OpenAlex.
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- Increased NMDARs in neurons and glutamine synthetase in astrocytes underlying autistic-like behaviors ofiScience · 2023Article
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- A molecular framework for autistic experiences: Mitochondrial allostatic load as a mediator between autism and psychopathology.Frontiers in psychiatry · 2022Article
- Symptomatic, Genetic, and Mechanistic Overlaps between Autism and Alzheimer's Disease.Biomolecules · 2021Review
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- The Novel Potential Therapeutic Utility of Montelukast in Alleviating Autistic Behavior Induced by Early Postnatal Administration of Thimerosal in Mice.Cellular and molecular neurobiology · 2021Article
- Pharmacological Manipulation of Wnt/β-Catenin Signaling Pathway in Human Neural Precursor Cells Alters Their Differentiation Potential and Neuronal Yield.Frontiers in molecular neuroscience · 2021Article
- Wnt/β-Catenin-Dependent Transcription in Autism Spectrum Disorders.Frontiers in molecular neuroscience · 2021Review
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- Novel Contribution of Secreted Amyloid-β Precursor Protein to White Matter Brain Enlargement in Autism Spectrum Disorder.Frontiers in psychiatry · 2019Review
- Current Trends of Microfluidic Single-Cell Technologies.International journal of molecular sciences · 2018Review
- A Statistical Framework for Mapping Risk Genes from De Novo Mutations in Whole-Genome-Sequencing Studies.American journal of human genetics · 2018Article
- Network-Based Identification of Altered Stem Cell Pluripotency and Calcium Signaling Pathways in Metastatic Melanoma.Medical sciences (Basel, Switzerland) · 2018Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autism and Alzheimer's disease (AD) are, respectively, neurodevelopmental and degenerative diseases with an increasing epidemiological burden. The AD-associated amyloid-β precursor protein-α has been shown to be elevated in severe autism, leading to the 'anabolic hypothesis' of its etiology. Here we performed a focused microarray analysis of genes belonging to NOTCH and WNT signaling cascades, as well as genes related to AD and apoptosis pathways in cerebellar samples from autistic individuals, to provide further evidence for pathological relevance of these cascades for autism. By using the limma package from R and false discovery rate, we demonstrated that 31% (116 out of 374) of the genes belonging to these pathways displayed significant changes in expression (corrected P-values <0.05), with mitochondria-related genes being the most downregulated. We also found upregulation of GRIN1, the channel-forming subunit of NMDA glutamate receptors, and MAP3K1, known activator of the JNK and ERK pathways with anti-apoptotic effect. Expression of PSEN2 (presinilin 2) and APBB1 (or F65) were significantly lower when compared with control samples. Based on these results, we propose a model of NMDA glutamate receptor-mediated ERK activation of α-secretase activity and mitochondrial adaptation to apoptosis that may explain the early brain overgrowth and disruption of synaptic plasticity and connectome in autism. Finally, systems pharmacology analyses of the model that integrates all these genes together (NOWADA) highlighted magnesium (Mg(2+)) and rapamycin as most efficient drugs to target this network model in silico. Their potential therapeutic application, in the context of autism, is therefore discussed.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.