Integration of genomic and transcriptomic layers in RNA‐Seq data leads to protein interaction modules with improved Alzheimer's disease associations DOI Open Access
Elif Düz, Atılay İlgün, Fatma Betül Bozkurt

et al.

European Journal of Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

Alzheimer's disease (AD) is the most common neurodegenerative disease, and it currently untreatable. RNA sequencing (RNA-Seq) commonly used in literature to identify AD-associated molecular mechanisms by analysing changes gene expression. RNA-Seq data can also be detect genomic variants, enabling identification of genes with a higher load deleterious variants patients compared controls. Here, we analysed AD datasets obtain differentially expressed pathogenic AD, combined them single list. We mapped these on human protein-protein interaction network discover subnetworks perturbed AD. Our results show that utilizing pathogenicity information from positively contributes disclosure AD-related mechanisms. Moreover, dividing discovered into highly connected modules reveals clearer picture altered pathways that, otherwise, would not captured. Repeating whole pipeline metabolic led confirming positive contribution enabled more detailed

Language: Английский

Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer’s Disease Pathogenesis—From Gut Microbiota and Viruses to Brain Biofilms DOI Creative Commons
Anna Onisiforou, Eleftheria G. Charalambous, Panos Zanos

et al.

Microorganisms, Journal Year: 2025, Volume and Issue: 13(1), P. 90 - 90

Published: Jan. 5, 2025

For decades, Alzheimer's Disease (AD) research has focused on the amyloid cascade hypothesis, which identifies amyloid-beta (Aβ) as primary driver of disease. However, consistent failure Aβ-targeted therapies to demonstrate efficacy, coupled with significant safety concerns, underscores need rethink our approach AD treatment. Emerging evidence points microbial infections environmental factors in pathoetiology. Although a definitive causal link remains unestablished, collective is compelling. This review explores unconventional perspectives and emerging paradigms regarding involvement pathogenesis, emphasizing gut-brain axis, brain biofilms, oral microbiome, viral infections. Transgenic mouse models show that gut microbiota dysregulation precedes Aβ accumulation, signaling pathways. Viral like Herpes Simplex Virus Type 1 (HSV-1) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may lead by modulating host processes immune system. peptide's antimicrobial function response infection might inadvertently promote AD. We discuss potential microbiome-based promising strategies for managing potentially preventing progression. Fecal transplantation (FMT) restores balance, reduces improves cognition preclinical models. Probiotics prebiotics reduce neuroinflammation plaques, while antiviral targeting HSV-1 vaccines shingles vaccine mitigate pathology. Developing effective treatments requires standardized methods identify measure patients, enabling personalized address individual contributions pathogenesis. Further needed clarify interactions between microbes Aβ, explore bacterial interplay, understand their broader effects translate these insights into clinical interventions.

Language: Английский

Citations

4
Association of Methyl Donor Nutrients’ Dietary Intake and Cognitive Impairment in the Elderly Based on the Intestinal Microbiome DOI Open Access
Qianqian Chen, Rui Fan,

Lixia Song

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 16(13), P. 2061 - 2061

Published: June 28, 2024

Globally, cognitive impairment (CI) is the leading cause of disability and dependency among elderly, presenting a significant public health concern. However, there currently deficiency in pharmacological interventions that can effectively cure or significantly reverse progression impairment. Methyl donor nutrients (MDNs), including folic acid, choline, vitamin B12, have been identified as potential enhancers function. Nevertheless, remains dearth comprehensive research investigating connection between dietary intake MDNs CI. In our study, we comprehensively assessed relationship MDNs’ CI older adults, utilizing 16S rRNA gene sequencing to investigate underlying mechanisms. The results showed an obvious difference methyl-donor nutritional quality index (MNQI) dementia (D) group dementia-free (DF) group. Specifically, was lower MNQI D than DF For gut microbiome, beta diversity flora exhibited higher levels high (HQ) opposed low (LQ) group, comparison Subsequently, performed correlation analysis examine relative abundance microbiota, MDNs, Montreal Cognitive Assessment (MoCA) scores, ultimately identifying ten genera with regulatory functions. Additionally, KEGG pathway analyses suggested one-carbon metabolism, chronic inflammation, DNA synthesis potentially serve pathways through which may be promising for influencing These implied might enhance function regulation microbiota homeostasis. This study offers recommendations prevention management elderly.

Language: Английский

Citations

4
Identification of critical genes and drug repurposing targets in entorhinal cortex of Alzheimer’s disease DOI
Arghavan Hosseinpouri, Khadijeh Sadegh, Zeinab Zarei‐Behjani

et al.

Neurogenetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: Feb. 10, 2025

Language: Английский

Citations

0
SFRP1 upregulation causes hippocampal synaptic dysfunction and memory impairment DOI Creative Commons
Guadalupe Pereyra,

María Inés Mateo,

Pablo Miaja

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115535 - 115535

Published: April 1, 2025

Impaired neuronal and synaptic function are hallmarks of early Alzheimer's disease (AD), preceding other neuropathological traits cognitive decline. We previously showed that SFRP1, a glial-derived protein elevated in AD brains from preclinical stages, contributes to progression, implicating glial factors pathogenesis. Here, we generate analyze transgenic mice overexpressing astrocytic SFRP1. SFRP1 accumulation causes dendritic defects adult mice, followed by impaired long-term potentiation decline, evident only when the animals age, thereby mimicking AD's structural-functional temporal distinction. This phenotype correlates with proteomic changes, including increased structural proteins like neurexin, which localizes close proximity cultured hippocampal neurons. conclude excessive hinders turnover, reducing plasticity-a mechanism may underlie synaptopathy observed prodromal patients.

Language: Английский

Citations

0
Resistance Exercise Training as a New Trend in Alzheimer’s Disease Research: From Molecular Mechanisms to Prevention DOI Open Access
Alexis Sepúlveda-Lara, Paulina Sepúlveda, Gabriel Nasri Marzuca-Nassr

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7084 - 7084

Published: June 27, 2024

Alzheimer's disease is a pathology characterized by the progressive loss of neuronal connections, which leads to gray matter atrophy in brain. most prevalent type dementia and has been classified into two types, early onset, associated with genetic factors, late environmental factors. One greatest challenges regarding high economic cost involved, why number studies aimed at prevention treatment have increased. possible approach use resistance exercise training, given that it shown neuroprotective effects disease, such as increasing cortical hippocampal volume, improving neuroplasticity, promoting cognitive function throughout life cycle. However, how training specifically prevents or ameliorates not fully characterized. Therefore, aim this review was identify molecular basis could prevent treat disease.

Language: Английский

Citations

2
One Path, Two Solutions: Network-Based Analysis Identifies Targetable Pathways for the Treatment of Comorbid Type II Diabetes and Neuropsychiatric Disorders DOI Creative Commons
Anna Onisiforou, Panos Zanos

Computational and Structural Biotechnology Journal, Journal Year: 2024, Volume and Issue: 23, P. 3610 - 3624

Published: Oct. 10, 2024

Language: Английский

Citations

2
Integration of genomic and transcriptomic layers in RNA‐Seq data leads to protein interaction modules with improved Alzheimer's disease associations DOI Open Access
Elif Düz, Atılay İlgün, Fatma Betül Bozkurt

et al.

European Journal of Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

Alzheimer's disease (AD) is the most common neurodegenerative disease, and it currently untreatable. RNA sequencing (RNA-Seq) commonly used in literature to identify AD-associated molecular mechanisms by analysing changes gene expression. RNA-Seq data can also be detect genomic variants, enabling identification of genes with a higher load deleterious variants patients compared controls. Here, we analysed AD datasets obtain differentially expressed pathogenic AD, combined them single list. We mapped these on human protein-protein interaction network discover subnetworks perturbed AD. Our results show that utilizing pathogenicity information from positively contributes disclosure AD-related mechanisms. Moreover, dividing discovered into highly connected modules reveals clearer picture altered pathways that, otherwise, would not captured. Repeating whole pipeline metabolic led confirming positive contribution enabled more detailed

Language: Английский

Citations

0