scholarly journals The role of overexpressed DYRK1A protein in the early onset of neurofibrillary degeneration in Down syndrome

2008 ◽  
Vol 116 (4) ◽  
pp. 391-407 ◽  
Author(s):  
Jerzy Wegiel ◽  
Karol Dowjat ◽  
Wojciech Kaczmarski ◽  
Izabela Kuchna ◽  
Krzysztof Nowicki ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Early Onset ◽  
Neurofibrillary Degeneration

scholarly journals P4-030: THE EARLY ONSET OF BRAIN INSULIN RESISTANCE IN DOWN SYNDROME: ROLE OF TRIPLICATED MIR802

2019 ◽  
Vol 15 ◽  
pp. P1286-P1286
Author(s):  
Eugenio Barone ◽  
Antonella Tramutola ◽  
Andrea Arena ◽  
Fabio Di Domenico ◽  
Elizabeth Head ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Down Syndrome ◽  
Early Onset ◽  
Brain Insulin ◽  
Brain Insulin Resistance

Exploring the Role of Aggregated Proteomes in the Pathogenesis of Alzheimer’s Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 1164-1173
Author(s):  
Siju Ellickal Narayanan ◽  
Nikhila Sekhar ◽  
Rajalakshmi Ganesan Rajamma ◽  
Akash Marathakam ◽  
Abdullah Al Mamun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Early Onset ◽  
Late Onset ◽  
Precursor Protein ◽  
Brain Disorder ◽  
Amyloid Aβ ◽  
T Tau

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

scholarly journals Characterization of Caenorhabditis elegans Homologs of the Down Syndrome Candidate Gene DYRK1A

Genetics ◽  
2003 ◽  
Vol 163 (2) ◽  
pp. 571-580 ◽  
Author(s):  
William B Raich ◽  
Celine Moorman ◽  
Clay O Lacefield ◽  
Jonah Lehrer ◽  
Dusan Bartsch ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Caenorhabditis Elegans ◽  
Trisomy 21 ◽  
Gene Dosage ◽  
Inducible Promoters ◽  
C Elegans ◽  
Dual Specificity ◽  
Specificity Protein

Abstract The pathology of trisomy 21/Down syndrome includes cognitive and memory deficits. Increased expression of the dual-specificity protein kinase DYRK1A kinase (DYRK1A) appears to play a significant role in the neuropathology of Down syndrome. To shed light on the cellular role of DYRK1A and related genes we identified three DYRK/minibrain-like genes in the genome sequence of Caenorhabditis elegans, termed mbk-1, mbk-2, and hpk-1. We found these genes to be widely expressed and to localize to distinct subcellular compartments. We isolated deletion alleles in all three genes and show that loss of mbk-1, the gene most closely related to DYRK1A, causes no obvious defects, while another gene, mbk-2, is essential for viability. The overexpression of DYRK1A in Down syndrome led us to examine the effects of overexpression of its C. elegans ortholog mbk-1. We found that animals containing additional copies of the mbk-1 gene display behavioral defects in chemotaxis toward volatile chemoattractants and that the extent of these defects correlates with mbk-1 gene dosage. Using tissue-specific and inducible promoters, we show that additional copies of mbk-1 can impair olfaction cell-autonomously in mature, fully differentiated neurons and that this impairment is reversible. Our results suggest that increased gene dosage of human DYRK1A in trisomy 21 may disrupt the function of fully differentiated neurons and that this disruption is reversible.

Early onset of overweight among children from low‐income families: The role of exclusive breastfeeding and maternal intake of ultra‐processed food

2021 ◽  
Author(s):  
Jayanne Mayara Magalhães Melo ◽  
Bruna Larine Lemos Fontes Silva Dourado ◽  
Risia Cristina Egito Menezes ◽  
Giovana Longo‐Silva ◽  
Jonas Augusto Cardoso Silveira
Keyword(s):  
Low Income ◽  
Exclusive Breastfeeding ◽  
Early Onset ◽  
Processed Food ◽  
Low Income Families

scholarly journals Novel TTLL5 Variants Associated with Cone-Rod Dystrophy and Early-Onset Severe Retinal Dystrophy

2021 ◽  
Vol 22 (12) ◽  
pp. 6410
Author(s):  
Vasily Smirnov ◽  
Olivier Grunewald ◽  
Jean Muller ◽  
Christina Zeitz ◽  
Carolin D. Obermaier ◽  
...  
Keyword(s):  
Early Onset ◽  
Retinal Dystrophy ◽  
Copy Number Variants ◽  
Cone Dystrophy ◽  
The Novel ◽  
Targeted Next Generation Sequencing ◽  
Large Deletions ◽  
Gene Panels ◽  
Generation Sequencing

Variants of the TTLL5 gene, which encodes tubulin tyrosine ligase-like family member five, are a rare cause of cone dystrophy (COD) or cone-rod dystrophy (CORD). To date, only a few TTLL5 patients have been clinically and genetically described. In this study, we report five patients harbouring biallelic variants of TTLL5. Four adult patients presented either COD or CORD with onset in the late teenage years. The youngest patient had a phenotype of early onset severe retinal dystrophy (EOSRD). Genetic analysis was performed by targeted next generation sequencing of gene panels and assessment of copy number variants (CNV). We identified eight variants, of which six were novel, including two large multiexon deletions in patients with COD or CORD, while the EOSRD patient harboured the novel homozygous p.(Trp640*) variant and three distinct USH2A variants, which might explain the observed rod involvement. Our study highlights the role of TTLL5 in COD/CORD and the importance of large deletions. These findings suggest that COD or CORD patients lacking variants in known genes may harbour CNVs to be discovered in TTLL5, previously undetected by classical sequencing methods. In addition, variable phenotypes in TTLL5-associated patients might be due to the presence of additional gene defects.

Neurobiological Elements of Cognitive Dysfunction in Down Syndrome: Exploring the Role of APP

2012 ◽  
Vol 71 (5) ◽  
pp. 403-409 ◽  
Author(s):  
Martha Millan Sanchez ◽  
Sietske N. Heyn ◽  
Devsmita Das ◽  
Sarah Moghadam ◽  
Kara J. Martin ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Cognitive Dysfunction

The role of germline mutations in the BRCA1/2 and mismatch repair genes in men ascertained for early-onset and/or familial prostate cancer

2015 ◽  
Vol 15 (1) ◽  
pp. 111-121 ◽  
Author(s):  
Sofia Maia ◽  
Marta Cardoso ◽  
Paula Paulo ◽  
Manuela Pinheiro ◽  
Pedro Pinto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mismatch Repair ◽  
Early Onset ◽  
Germline Mutations ◽  
Mismatch Repair Genes ◽  
Repair Genes
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