Targeting Alzheimer’s Disease: The Critical Crosstalk between the Liver and Brain DOI Open Access
Zhihai Huang, Hung Wen Lin, Quanguang Zhang

et al.

Nutrients, Journal Year: 2022, Volume and Issue: 14(20), P. 4298 - 4298

Published: Oct. 14, 2022

Alzheimer’s disease (AD), an age-related neurodegenerative disorder, is currently incurable. Imbalanced amyloid-beta (Aβ) generation and clearance are thought to play a pivotal role in the pathogenesis of AD. Historically, strategies targeting Aβ have typically focused on central clearance, but with limited clinical success. Recently, contribution peripheral systems, particularly liver, has sparked increased interest. In addition, AD presents pathological features similar those metabolic syndrome, critical involvement brain energy disturbances this been recognized. More importantly, liver may be key regulator these abnormalities, far beyond our past understanding. Here, we review recent animal findings indicating that dysfunction represents early event pathophysiology. We further propose compromised by aberrant hepatic physiological processes contribute neurodegeneration. The synthesis product, fibroblast growth factor 21 (FGF21), management also discussed. A deeper understanding communication between lead new opportunities for diagnosis treatment

Language: Английский

Metabolic mechanisms in physiological and pathological cardiac hypertrophy: new paradigms and challenges DOI
Julia Ritterhoff, Rong Tian

Nature Reviews Cardiology, Journal Year: 2023, Volume and Issue: 20(12), P. 812 - 829

Published: May 26, 2023

Language: Английский

Citations

94
Inhibition of fatty acid uptake by TGR5 prevents diabetic cardiomyopathy DOI Creative Commons
H J Wang, Jiaxing Wang, Hao Cui

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(6), P. 1161 - 1177

Published: May 2, 2024

Language: Английский

Citations

25
Current status and future perspectives of FGF21 analogues in clinical trials DOI
Zara Siu Wa Chui, Qing Shen, Aimin Xu

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(5), P. 371 - 384

Published: Feb. 28, 2024

Language: Английский

Citations

19
Sirt5 improves cardiomyocytes fatty acid metabolism and ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via CPT2 de-succinylation DOI Creative Commons
Maoxiong Wu, Jing Tan, Zhengyu Cao

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 73, P. 103184 - 103184

Published: May 5, 2024

The disruption of the balance between fatty acid (FA) uptake and oxidation (FAO) leads to cardiac lipotoxicity, serving as driving force behind diabetic cardiomyopathy (DbCM). Sirtuin 5 (Sirt5), a lysine de-succinylase, could impact diverse metabolic pathways, including FA metabolism. Nevertheless, precise roles Sirt5 in lipotoxicity DbCM remain unknown. This study aims elucidate role underlying mechanism context DbCM. expression myocardial was found be modestly elevated heart failure patients mice. Cardiac dysfunction, hypertrophy were exacerbated by ablation but improved forced Notably, deficiency impaired FAO without affecting capacity heart, leading accumulation intermediate metabolites, which mainly included medium- long-chain acyl-carnitines. Mechanistically, succinylomics analyses identified carnitine palmitoyltransferase 2 (CPT2), crucial enzyme involved reconversion acyl-carnitines acyl-CoA facilitating FAO, functional succinylated substrate mediator Sirt5. Succinylation Lys424 CPT2 significantly increased deficiency, inactivation its enzymatic activity subsequent K424R mutation, mitigated succinylation modification, counteracted reduction mediated thereby attenuating knockout-induced impairment lipid deposition. impairs through CPT2. underscores potential therapeutic targets for addressing

Language: Английский

Citations

19
Mitochondrial Dysfunction in HFpEF: Potential Interventions Through Exercise DOI
Xinxin Cui, Michail Spanos, Cuimei Zhao

et al.

Journal of Cardiovascular Translational Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 25, 2025

Language: Английский

Citations

4
FGF-based drug discovery: advances and challenges DOI
Gaozhi Chen, Lingfeng Chen, Xiaokun Li

et al.

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Language: Английский

Citations

4
Roles of Sirtuins in Cardiovascular Diseases: Mechanisms and Therapeutics DOI

Yang-Nan Ding,

Hui-Yu Wang,

Xiaofeng Chen

et al.

Circulation Research, Journal Year: 2025, Volume and Issue: 136(5), P. 524 - 550

Published: Feb. 27, 2025

Cardiovascular diseases (CVDs) are experiencing a rapid surge and widely recognized as the leading cause of mortality in current aging society. Given multifactorial etiology CVDs, understanding intricate molecular cellular mechanisms is imperative. Over past 2 decades, many scientists have focused on Sirtuins, family nicotinamide adenine dinucleotide–dependent deacylases. Sirtuins highly conserved across species, from yeasts to primates, play crucial role linking diseases. participate nearly all key physiological pathological processes, ranging embryogenic development stress response aging. Abnormal expression activity exist aging-related diseases, while their activation has shown efficacy mitigating these (eg, CVDs). In terms research, this field maintained fast, sustained growth recent years, fundamental studies clinical trials. review, we present comprehensive, up-to-date discussion biological functions roles regulating cardiovascular biology CVDs. Furthermore, highlight latest advancements utilizing Sirtuin-activating compounds dinucleotide boosters potential pharmacological targets for preventing treating The unresolved issues field—from chemicobiological regulation Sirtuin-targeted CVD investigations—are also discussed. This timely review could be critical updated knowledge Sirtuin CVDs facilitating accessibility Sirtuin-targeting interventions.

Language: Английский

Citations

3
The role of mitochondria in myocardial damage caused by energy metabolism disorders: From mechanisms to therapeutics DOI
Aolin Li, Lu Lian,

Xin-nong Chen

et al.

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 208, P. 236 - 251

Published: Aug. 9, 2023

Language: Английский

Citations

35
Nrf2 signaling in diabetic nephropathy, cardiomyopathy and neuropathy: Therapeutic targeting, challenges and future prospective DOI Creative Commons
Mehrdad Hashemi, Mohammad Arad Zandieh,

Setayesh Ziaolhagh

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2023, Volume and Issue: 1869(5), P. 166714 - 166714

Published: April 5, 2023

Language: Английский

Citations

32
Mitochondrial quality control in health and cardiovascular diseases DOI Creative Commons
Asli E. Atici, Timothy R. Crother, Magali Noval Rivas

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Nov. 6, 2023

Cardiovascular diseases (CVDs) are one of the primary causes mortality worldwide. An optimal mitochondrial function is central to supplying tissues with high energy demand, such as cardiovascular system. In addition producing ATP a power source, mitochondria also heavily involved in adaptation environmental stress and fine-tuning tissue functions. Mitochondrial quality control (MQC) through fission, fusion, mitophagy, biogenesis ensures clearance dysfunctional preserves homeostasis tissues. Furthermore, generate reactive oxygen species (ROS), which trigger production pro-inflammatory cytokines regulate cell survival. dysfunction has been implicated multiple CVDs, including ischemia-reperfusion (I/R), atherosclerosis, heart failure, cardiac hypertrophy, hypertension, diabetic genetic cardiomyopathies, Kawasaki Disease (KD). Thus, MQC pivotal promoting health. Here, we outline mechanisms discuss current literature on CVDs.

Language: Английский

Citations

24