Matrix metalloproteinase-degraded type I collagen is associated with
            <i>APOE/TOMM40</i>
            variants and preclinical dementia

Tang, Man-Hung Eric; Blair, Joseph; Bager, Cecilie L.; Bay‐Jensen, Anne‐Christine; Henriksen, Kim; Christiansen, Claus; Karsdal, Morten A.

doi:10.1212/nxg.0000000000000508

Cited by 9 publications

(5 citation statements)

References 34 publications

(39 reference statements)

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“…Scanning of the GWAS catalog database for associations of the 23 g and EF common SNPs with other traits revealed that 8 SNPs have been previously associated with biological (hippocampal [ 58 ] and other brain regions volume [ 59 ], cortical surface area [ 60 ], mean reticulocyte volume [ 61 ], serum type 1 collagen metabolite levels [ 62 ], cerebral amyloid deposition [ 63 ]), psychological, psychiatric and neurological traits (anxiety & neuroticism [ 64 ], schizophrenia [ 65 , 66 ], family history of Alzheimer’s disease [ 67 ]) cognition-related traits; as well as being associated with other behavioural and functional traits (asthma [ 68 ], alcohol consumption [ 69 ], sedentary lifestyle [ 70 ], household income [ 71 ]) ( Table 4 ).…”

Section: Resultsmentioning

confidence: 99%

General intelligence and executive functioning are overlapping but separable at genetic and molecular pathway levels: An analytical review of existing GWAS findings

Ciobanu

Stankov²,

Schubert³

et al. 2022

PLoS ONE

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Understanding the genomic architecture and molecular mechanisms of cognitive functioning in healthy individuals is critical for developing tailored interventions to enhance cognitive functioning, as well as for identifying targets for treating impaired cognition. There has been substantial progress in uncovering the genetic composition of the general cognitive ability (g). However, there is an ongoing debate whether executive functioning (EF)–another key predictor of cognitive health and performance, is separable from general g. To provide an analytical review on existing findings on genetic influences on the relationship between g and EF, we re-analysed a subset of genome-wide association studies (GWAS) from the GWAS catalogue that used measures of g and EF as outcomes in non-clinical populations. We identified two sets of single nucleotide polymorphisms (SNPs) associated with g (1,372 SNPs across 12 studies), and EF (300 SNPs across 5 studies) at p<5x10-6. A comparative analysis of GWAS-identified g and EF SNPs in high linkage disequilibrium (LD), followed by pathway enrichment analyses suggest that g and EF are overlapping but separable at genetic variant and molecular pathway levels, however more evidence is required to characterize the genetic overlap/distinction between the two constructs. While not without limitations, these findings may have implications for navigating further research towards translatable genetic findings for cognitive remediation, enhancement, and augmentation.

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Section: Resultsmentioning

confidence: 99%

General intelligence and executive functioning are overlapping but separable at genetic and molecular pathway levels: An analytical review of existing GWAS findings

Ciobanu

Stankov²,

Schubert³

et al. 2022

PLoS ONE

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show abstract

“…Notably, collagen metabolism pathways were also prominently involved in our BPAN disease model, with interesting links to neurodegeneration. 67, 68, 69, 70 Lack of COL1A1 and COL6A1 are associated with increased spontaneous apoptosis, abnormal autophagy and increased vulnerability to oxidative stress. 67, 70 Genome-wide association studies have identified a link between dementia and abnormal collagen I metabolism.…”

Section: Discussionmentioning

confidence: 99%

Cardiac glycosides restore autophagy flux in an iPSC-derived neuronal model of WDR45 deficiency

Papandreou,

Singh,

Gianfrancesco

et al. 2023

Preprint

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Beta-Propeller Protein-Associated Neurodegeneration (BPAN) is one of the commonest forms of Neurodegeneration with Brain Iron Accumulation, caused by mutations in the gene encoding the autophagy-related protein, WDR45. The mechanisms linking autophagy, iron overload and neurodegeneration in BPAN are poorly understood and, as a result, there are currently no disease-modifying treatments for this progressive disorder. We have developed a patient-derived, induced pluripotent stem cell (iPSC)-based midbrain dopaminergic neuronal cell model of BPAN (3 patient, 2 age-matched controls and 2 isogenic control lines) which shows defective autophagy and aberrant gene expression in key neurodegenerative, neurodevelopmental and collagen pathways. A high content imaging-based medium-throughput blinded drug screen using the FDA-approved Prestwick library identified 5 cardiac glycosides that both corrected disease-related defective autophagosome formation and restored BPAN-specific gene expression profiles. Our findings have clear translational potential and emphasise the utility of iPSC-based modelling in elucidating disease pathophysiology and identifying targeted therapeutics for early-onset monogenic disorders.

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“…Coating materials with green bioactive substances serves not only to enhance bioactivity but also plays a crucial role in reducing the inherent toxicity of metal NPs. 19 Furthermore, collagen-based biomaterials are frequently utilized for safeguarding and restoring the AHD. 20 These materials made from collagen offer support and create a conductive microenvironment that encourages the growth of axons.…”

Section: Introductionmentioning

confidence: 99%

Exploring Bimetallic Nanoparticles in Alzheimer’s Therapy: A Novel Bio-Assisted Synthesis with Multitarget Potential

Gülseren,

Demirsoy,

Şeker

et al. 2024

Mol. Pharmaceutics

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Unlocking the potential of metal nanoparticles (NPs) in biomedical applications represents a leading endeavor in contemporary research. Among these, gold NPs (AuNPs) and silver NPs (AgNPs) have shown promising strides in combatting complex neurodegenerative ailments like Alzheimer's disease. Yet, the unexplored realm of bimetallic Au/Ag-NP harbors immense potential, concealing undiscovered opportunities for enhanced therapeutic effectiveness through the synergistic interaction of metal ions. Nonetheless, the limitations of traditional synthesis methods have restricted the preparation, biocompatibility, and versatility of these NPs, prompting an urgent requirement for innovative approaches. Biobased synthetic methodologies have emerged as a noteworthy solution to address these challenges. Our study ventures into uncharted terrain, harnessing collagen-mimicking peptide nanofibers as a bioactive template for the synthesis of bimetallic NPs. These green NPs exhibit remarkable activity in inhibiting amyloid β (Aβ) protein aggregation with almost 74% inhibition, surpassing the individual impacts of Au and Ag NPs, which show inhibition percentages of 66 and 43, respectively. The bimetallic Au/Ag-NPs not only demonstrate powerful inhibition of Aβ, but they also demonstrate inhibitory activity against esterase (∼50%) and against reactive oxygen species (ROS) (∼75%), metamorphosing into multifaceted therapeutic agents for Alzheimer's disease. Au/Ag-NPs have proven highly beneficial in surpassing cellular barriers, as evidenced by studies on tissue penetration, 3D uptake, and endosomal escape, and these attributes also hold promise for the future treatment modalities. The findings indicate that the intrinsic traits of Au/Ag-NPs provide numerous mechanistic benefits, such as inhibiting Aβ and acetylcholinesterase (AChE), and reducing stress related to ROS, in addition to their advantageous internalization properties. This research represents a notable advancement in the development of multitargeted treatments for neurodegenerative disorders using bimetallic NPs, diverging from the prevalent emphasis on AuNPs in the current literature.

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Matrix metalloproteinase-degraded type I collagen is associated with APOE/TOMM40 variants and preclinical dementia

Cited by 9 publications

References 34 publications

General intelligence and executive functioning are overlapping but separable at genetic and molecular pathway levels: An analytical review of existing GWAS findings

General intelligence and executive functioning are overlapping but separable at genetic and molecular pathway levels: An analytical review of existing GWAS findings

Cardiac glycosides restore autophagy flux in an iPSC-derived neuronal model of WDR45 deficiency

Exploring Bimetallic Nanoparticles in Alzheimer’s Therapy: A Novel Bio-Assisted Synthesis with Multitarget Potential

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