Association Between Hypoxia‐Inducible Factor‐1α and Neurological Diseases: A Bidirectional Two‐Sample Mendelian Randomization Analysis DOI Creative Commons

Jing Liang,

Xiaoyan Du, Mengfei Wang

и другие.

Brain and Behavior, Год журнала: 2025, Номер 15(3)

Опубликована: Фев. 28, 2025

ABSTRACT Background Previous studies have suggested that hypoxia‐inducible factor 1‐α (HIF‐1α) exerted multiple effects on different central nervous system disorders. However, it is still uncertain whether plasma HIF‐1α can be a causal indicator for the relevant diseases. This study aimed to test causality relationship between and neurological diseases, including cerebrovascular migraines, neurodegenerative diseases with Mendelian randomization (MR) method. Methods Single‐nucleotide polymorphisms (SNPs) genetically representing were screened as instrumental variables (IVs). Summary‐level data disorder from genome‐wide association (GWAS) identified outcomes. The IVs outcomes determined via major analysis of inverse‐variance‐weighted (IVW) reverse direction was also performed investigate possibility causation. Results findings revealed associated cardioembolic stroke (CES) (OR = 0.885; 95% confidence interval [CI] 0.796–0.985, p 0.026), migraine 0.941, CI 0.888–0.998, 0.041), drug‐induced without aura (MOA) 0.586, 0.375–0.916, 0.019). There no in subarachnoid hemorrhage (SAH), other subtype, reverse‐MR above‐stated did not effect levels. Sensitivity validation analyses support above results are stable. Conclusions Our research indicated may risk CES, MOA, providing new insights those disease prevention therapeutic approaches.

Язык: Английский

Inflammasomes in Alzheimer’s Progression: Nrf2 as a Preventive Target DOI Creative Commons

Rubén López-Hernández,

María Magdalena de la Torre-Álamo,

Borja García‐Bueno

и другие.

Antioxidants, Год журнала: 2025, Номер 14(2), С. 121 - 121

Опубликована: Янв. 21, 2025

Current knowledge about Alzheimer’s disease highlights the accumulation of β-amyloid plaques (Aβ1–42) and neurofibrillary tangles composed hyperphosphorylated Tau, which lead to loss neuronal connections. Microglial activation release inflammatory mediators play a significant role in progression pathology. Recent advances have identified involvement inflammasomes, particularly NOD-like receptor NLR family pyrin domain containing 3 (NLRP3), whose promotes proinflammatory cytokines triggers pyroptosis, exacerbating neuroinflammation. Aggregates Aβ1–42 Tau been shown activate these while apoptosis-associated speck-like protein (ASC) components form aggregates that further accelerate Aβ aggregation. Defects autophagic clearance inflammasomes also implicated disease, contributing sustained inflammation. This review explores strategies counteract inflammation Alzheimer’s, emphasizing degradation ASC specks inhibition NLRP3 inflammasome activation. Notably, nuclear factor erythroid 2-related 2 (Nrf2) transcription emerges as promising therapeutic target due its dual mitigating oxidative stress directly inhibiting formation. By reducing inflammasome-driven inflammation, Nrf2 offers potential for addressing neuroinflammatory aspects disease.

Язык: Английский

Процитировано

0
Association Between Hypoxia‐Inducible Factor‐1α and Neurological Diseases: A Bidirectional Two‐Sample Mendelian Randomization Analysis DOI Creative Commons

Jing Liang,

Xiaoyan Du, Mengfei Wang

и другие.

Brain and Behavior, Год журнала: 2025, Номер 15(3)

Опубликована: Фев. 28, 2025

ABSTRACT Background Previous studies have suggested that hypoxia‐inducible factor 1‐α (HIF‐1α) exerted multiple effects on different central nervous system disorders. However, it is still uncertain whether plasma HIF‐1α can be a causal indicator for the relevant diseases. This study aimed to test causality relationship between and neurological diseases, including cerebrovascular migraines, neurodegenerative diseases with Mendelian randomization (MR) method. Methods Single‐nucleotide polymorphisms (SNPs) genetically representing were screened as instrumental variables (IVs). Summary‐level data disorder from genome‐wide association (GWAS) identified outcomes. The IVs outcomes determined via major analysis of inverse‐variance‐weighted (IVW) reverse direction was also performed investigate possibility causation. Results findings revealed associated cardioembolic stroke (CES) (OR = 0.885; 95% confidence interval [CI] 0.796–0.985, p 0.026), migraine 0.941, CI 0.888–0.998, 0.041), drug‐induced without aura (MOA) 0.586, 0.375–0.916, 0.019). There no in subarachnoid hemorrhage (SAH), other subtype, reverse‐MR above‐stated did not effect levels. Sensitivity validation analyses support above results are stable. Conclusions Our research indicated may risk CES, MOA, providing new insights those disease prevention therapeutic approaches.

Язык: Английский

Процитировано

0