Calcium bridges built by mitochondria-associated endoplasmic reticulum membranes: potential targets for neural repair in neurological diseases DOI Creative Commons

Yichen Peng,

Li Zhou,

Yaju Jin

и другие.

Neural Regeneration Research, Год журнала: 2024, Номер 20(12), С. 3349 - 3369

Опубликована: Ноя. 13, 2024

The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions metabolic levels. Mitochondria-associated endoplasmic reticulum membranes serve as physical contact channels the membrane mitochondrial outer membrane, formed by various proteins protein complexes. This microstructural domain mediates several specialized functions, including calcium (Ca 2+ ) signaling, autophagy, morphology, oxidative stress response, apoptosis. Notably, dysregulation Ca signaling mediated mitochondria-associated is critical factor pathogenesis neurological diseases. Certain or complexes within these directly indirectly regulate distance mitochondria, well transduction signaling. Conversely, influences other membrane-associated functions. These can vary significantly across different diseases—such ischemic stroke, traumatic brain injury, Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis, Huntington’s disease—and their respective stages progression. Targeted modulation disease-related pathways functional enhance function promote regeneration repair damaged neurons. Therefore, membranes-mediated pivotal pathological progression diseases represents significant potential therapeutic target. review focuses on effects distinct roles diseases, specifically highlighting early protective neuronal damage that result from prolonged overload deficiency. article provides comprehensive analysis mechanisms contributing to exploration targets for promoting neuroprotection nerve repair.

Язык: Английский

Mitochondria‐Related Genome‐Wide Mendelian Randomization Identifies Putatively Causal Genes for Neurodegenerative Diseases DOI Open Access
Zheyi Wang, Yize Sun,

Zetai Bai

и другие.

Movement Disorders, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Mitochondrial dysfunction is increasingly recognized as a key factor in neurodegenerative diseases (NDDs), underscoring the therapeutic potential of targeting mitochondria-related genes. This study aimed to identify novel biomarkers and drug targets for these through comprehensive analysis that integrated genome-wide Mendelian randomization (MR) with genes associated mitochondrial function. Using existing publicly available association studies (GWAS) summary statistics data on 1136 genes, we initially identified subset related function exhibited significant associations NDDs. We then conducted colocalization summary-data-based (SMR) analyses using expression quantitative trait loci (eQTL) validate causal role candidate Additionally, assessed druggability encoded proteins prioritize further exploration. Genetically predicted levels 10 were found be significantly risk Elevated DMPK LACTB2 increased Alzheimer's disease risk. Higher NDUFAF2, BCKDK, MALSU1, along lower TTC19, raised Parkinson's ACLY both amyotrophic lateral sclerosis multiple (MS) risks, while decreased MCL1, TOP3A, VWA8 MS These primarily impact energy metabolism. Notably, several druggable protein are being explored NDDs treatment. data-driven MR demonstrated this could serve pharmacological prevention treatment © 2025 International Parkinson Movement Disorder Society.

Язык: Английский

Процитировано

3
Phosphoglycerate mutase 5 exacerbates alcoholic cardiomyopathy in male mice by inducing prohibitin‐2 dephosphorylation and impairing mitochondrial quality control DOI Creative Commons
Jun Tao, Junxiong Qiu, Junmeng Zheng

и другие.

Clinical and Translational Medicine, Год журнала: 2024, Номер 14(8)

Опубликована: Авг. 1, 2024

The induction of mitochondrial quality control (MQC) mechanisms is essential for the re-establishment homeostasis and cellular bioenergetics during periods stress. Although MQC activation has cardioprotective effects in various cardiovascular diseases, its precise role regulatory alcoholic cardiomyopathy (ACM) remain incompletely understood.

Язык: Английский

Процитировано

9
Computational studies on the functional and structural impact of pathogenic mutations in enzymes DOI Open Access
Upeksha C. Dissanayake, Alice C. Roy, Yazdan Maghsoud

и другие.

Protein Science, Год журнала: 2025, Номер 34(4)

Опубликована: Март 21, 2025

Enzymes are critical biological catalysts involved in maintaining the intricate balance of metabolic processes within living organisms. Mutations enzymes can result disruptions to their functionality that may lead a range diseases. This review focuses on computational studies investigate effects disease-associated mutations various enzymes. Through molecular dynamics simulations, multiscale calculations, and machine learning approaches, provide detailed insights into how impact enzyme structure, dynamics, catalytic activity. emphasizes increasing simulations understanding mechanisms behind (dis)function by highlighting application key methodologies selected examples, aiding prediction mutation development therapeutic strategies.

Язык: Английский

Процитировано

0
Parkinson’s Disease: The Neurodegenerative Enigma Under the “Undercurrent” of Endoplasmic Reticulum Stress DOI Open Access
Xiangrui Kong, Tingting Liu, Jianshe Wei

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3367 - 3367

Опубликована: Апрель 3, 2025

Parkinson's disease (PD), a prevalent neurodegenerative disorder, demonstrates the critical involvement of endoplasmic reticulum stress (ERS) in its pathogenesis. This review comprehensively examines role and molecular mechanisms ERS PD. represents cellular response triggered by imbalances (ER) homeostasis, induced factors such as hypoxia misfolded protein aggregation, which activate unfolded (UPR) through inositol-requiring enzyme 1 (IRE1), kinase R-like (PERK), activating transcription factor 6 (ATF6) pathways. Clinical, animal model, studies have consistently demonstrated strong association between PD ERS. Abnormal expression ERS-related molecules patients' brains cerebrospinal fluid (CSF) correlates with progression. In models (e.g., Drosophila mice), inhibition alleviates dopaminergic neuronal damage. Cellular experiments reveal that PD-mimicking pathological conditions induce ERS, while interactions mitochondrial dysfunction promote apoptosis. Mechanistically, (1) aggregation α-synuclein (α-syn) mutually reinforce neuron damage; (2) leucine-rich repeat 2 (LRRK2) gene mutations thrombospondin-1 (THBS1)/transforming growth beta (TGF-β1) interactions; (3) Parkin PTEN-induced (PINK1) regulate Furthermore, interacts dysfunction, oxidative stress, neuroinflammation to exacerbate injury. Emerging therapeutic strategies show significant potential, including artificial intelligence (AI)-assisted drug design targeting pathways precision medicine approaches exploring non-pharmacological interventions personalized electroacupuncture. Future research should focus on elucidating identifying novel targets develop more effective treatments for patients, ultimately improving their quality life.

Язык: Английский

Процитировано

0
Loss of NgBR causes neuronal damage through decreasing KAT7-mediated RFX1 acetylation and FGF1 expression DOI Creative Commons
Yuwei Hu, Yanni Ma, Lele Liu

и другие.

Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)

Опубликована: Апрель 7, 2025

Parkinson's disease (PD) is a common neurodegenerative movement disorder characterized by dopaminergic neuron loss in the substantia nigra pars compacta and striatal dopamine depletion. The NUS1 gene, which encodes neurite outgrowth inhibitor B receptor (NgBR), has been recently identified as novel risk gene for PD. However, its roles mechanism neurodegeneration are still unclear. Here, we demonstrate that NgBR deficiency triggers neuronal damage through KAT7/RFX1/FGF1 axis. RNA sequencing experimental verification revealed depletion downregulates expression secretion of fibroblast growth factor 1 (FGF1), led to inactivation PI3K/AKT signaling pathway. Mechanistically, deletion suppresses lysine acetyltransferase 7 (KAT7) expression, impairing KAT7-mediated acetylation regulatory X1 (RFX1), transcriptional repressor FGF1. This stabilized RFX1 blocking proteasomal degradation, thereby suppressing FGF1 transcription. Crucially, exogenous rescued AKT mitigated NgBR-deficient models. Our findings establish NgBR-KAT7-RFX1 axis controlling FGF1-dependent neuroprotection, promotes understanding PD pathogenesis highlights supplementation potential therapeutic strategy.

Язык: Английский

Процитировано

0
Glutathione S-transferase: A keystone in Parkinson's disease pathogenesis and therapy DOI

Pratyush Padhan,

Simran Simran,

Neeraj Kumar

и другие.

Molecular and Cellular Neuroscience, Год журнала: 2024, Номер unknown, С. 103981 - 103981

Опубликована: Дек. 1, 2024

Язык: Английский

Процитировано

2
Protective effects of Parkin knockout on asthma-induced changes in juvenile mice: inflammation, airway resistance, and oxidative stress DOI

Hui-Fang Zhan,

Weijun Lin

Journal of Asthma, Год журнала: 2024, Номер unknown, С. 1 - 10

Опубликована: Сен. 13, 2024

This study aimed to explore the effects of Parkin (Prkn) knockout in a juvenile mouse model asthma.

Язык: Английский

Процитировано

1
Methamphetamine Increases Tubulo-Vesicular Areas While Dissipating Proteins from Vesicles Involved in Cell Clearance DOI Open Access
Gloria Lazzeri, Paola Lenzi, Carla L. Busceti

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9601 - 9601

Опубликована: Сен. 4, 2024

Cytopathology induced by methamphetamine (METH) is reminiscent of degenerative disorders such as Parkinson’s disease, and it characterized membrane organelles arranged in tubulo-vesicular structures. These areas, appearing clusters vesicles, have never been defined concerning the presence specific organelles. Therefore, present study aimed to identify relative absolute area membrane-bound following a moderate dose (100 µM) METH administered catecholamine-containing PC12 cells. Organelles antigens were detected immunofluorescence, they further quantified plain electron microscopy situ stoichiometry. This analysis indicated an increase autophagosomes damaged mitochondria along with decrease lysosomes healthy mitochondria. Following METH, severe dissipation hallmark proteins from their own vesicles was measured. In fact, amounts LC3 p62 reduced within autophagy vacuoles compared whole cytosol. Similarly, LAMP1 Cathepsin-D reduced. findings suggest loss compartmentalization confirm competence cell clearing during catecholamine degeneration. Such entropy consistent energy stores, which routinely govern appropriate subcellular compartmentalization.

Язык: Английский

Процитировано

0
Calcium bridges built by mitochondria-associated endoplasmic reticulum membranes: potential targets for neural repair in neurological diseases DOI Creative Commons

Yichen Peng,

Li Zhou,

Yaju Jin

и другие.

Neural Regeneration Research, Год журнала: 2024, Номер 20(12), С. 3349 - 3369

Опубликована: Ноя. 13, 2024

The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions metabolic levels. Mitochondria-associated endoplasmic reticulum membranes serve as physical contact channels the membrane mitochondrial outer membrane, formed by various proteins protein complexes. This microstructural domain mediates several specialized functions, including calcium (Ca 2+ ) signaling, autophagy, morphology, oxidative stress response, apoptosis. Notably, dysregulation Ca signaling mediated mitochondria-associated is critical factor pathogenesis neurological diseases. Certain or complexes within these directly indirectly regulate distance mitochondria, well transduction signaling. Conversely, influences other membrane-associated functions. These can vary significantly across different diseases—such ischemic stroke, traumatic brain injury, Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis, Huntington’s disease—and their respective stages progression. Targeted modulation disease-related pathways functional enhance function promote regeneration repair damaged neurons. Therefore, membranes-mediated pivotal pathological progression diseases represents significant potential therapeutic target. review focuses on effects distinct roles diseases, specifically highlighting early protective neuronal damage that result from prolonged overload deficiency. article provides comprehensive analysis mechanisms contributing to exploration targets for promoting neuroprotection nerve repair.

Язык: Английский

Процитировано

0